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    Carboplatin

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    Sep.11.2024

    CARBOplatin

    Indications/Dosage

    Labeled

    • ovarian cancer

    NOTE: The Society of Gynecologic Oncology (SGO) has issued a statement detailing platinum dosing and sparing recommendations to overcome challenges of limited drug availability. This statement and disease-specific recommendations can be found at https://www.sgo.org/chemotherapy-drug-shortage/.

     

    Carboplatin Dosing with the Calvert equation:[25916]

    NOTE: For all equations, AUC (area under the plasma concentration vs. time curve) is expressed in mg/ml x min and GFR (glomerular filtration rate) in ml/min.

     

    The GFR should be calculated using creatinine clearance determined by actual measurements or estimated by using the Cockroft-Gault or Jeliffe methods. It should be noted that these methods of determining creatinine clearance may not be as accurate, especially in patients with renal dysfunction or patients with low body weight, as the (51)Cr-EDTA method used in the original study. Currently, (51)Cr-EDTA is not available in the United States. The following are general recommendations for target AUC; however, exact dosing guidelines have not been established and may vary depending upon the disease state and protocol.

    • For chemotherapy naive patients receiving carboplatin: A target AUC of 6-8 mg/ml x min is recommended.
    • For previously treated patients receiving carboplatin alone: An AUC of 4-6 mg/ml x min is recommended.
    • For patients receiving carboplatin with other antineoplastics: An AUC of 4-7 mg/ml x min is recommended.

    NOTE: By the end of 2010, all clinical laboratories in the US will use the standardized Isotope Dilution Mass Spectrometry (IDMS) method to measure serum creatinine. Compared to older methods of measuring serum creatinine, the IDMS method may underestimate serum creatinine when values are relatively low (e.g. about 0.7 mg/dl). This could result in an overestimation of GFR in patients with normal renal function and when using the Calvert formula for carboplatin dosing (see below), may result in a higher than desired dose and increased drug-related toxicity. If a patient's GFR is calculated based on a serum creatinine measured using the IDMS method, the FDA recommends that physicians consider capping the dose of carboplatin for desired exposure to avoid potential overdosing. Based on the Calvert formula, maximum doses can be calculated as follows:

    Target AUC = 6, the maximum dose is 6 x 150 = 900 mg

    Target AUC = 5, the maximum dose is 5 x 150 = 750 mg

    Target AUC = 4, the maximum dose is 4 x 150 = 600 mg

    Maximum dose recommendations are based on a maximum estimated GFR = 125 ml/min. Higher estimated GFR values should not be used.[42067]

     

    Adults: The total carboplatin dose in mg for adults may be calculated using the Calvert equation:[25916]

    Total dose (mg) = target AUC x (GFR + 25)

     

    Children: The following equation should be used to calculate carboplatin dosage (mg/m2) in children. This equation accounts for differences in the renal elimination of carboplatin between adults and children:[25916]

    Total dose (mg/m2) = target AUC x [(0.93 x GFR) + 15]

    Off-Label

    • acute lymphocytic leukemia (ALL)
    • bladder cancer
    • breast cancer
    • endometrial cancer
    • glioblastoma multiforme
    • head and neck cancer
    • malignant glioma
    • mesothelioma
    • neuroblastoma
    • non-Hodgkin's lymphoma (NHL)
    • non-small cell lung cancer (NSCLC)
    • small cell lung cancer (SCLC)
    • stem cell transplant preparation
    • testicular cancer
    • thymic carcinoma
    • thymoma
    • urothelial carcinoma
    • Wilms' tumor
    † Off-label indication

    For the treatment of ovarian cancer

    for the first-line treatment of or palliative treatment of recurrent advanced ovarian cancer

    Intravenous dosage

    Adults

    For patients with previously untreated ovarian cancer, administer carboplatin 300 mg/m2 IV on day 1 in combination with cyclophosphamide (600 mg/m2 IV on day 1), repeated every 4 weeks for 6 cycles. For patients with recurrent ovarian cancer, administer single-agent carboplatin 360 mg/m2 IV (or AUC 5 to 6) on day 1, repeated every 4 weeks. Dosage adjustments should be made according to the lowest post-treatment platelet or neutrophil value as assessed by weekly blood counts.[29203]

    Intraperitoneal dosage†

    Adults

    200 to 650 mg/m2 intraperitoneally every 4 to 6 weeks has been studied. In 1 trial, 350 mg/m2 intraperitoneally with cyclophosphamide IV every 3 to 4 weeks resulted in similar response and survival rates as carboplatin 350 mg/m2 IV and cyclophosphamide IV with less myelotoxicity.[25918]

    for the first-line treatment of ovarian cancer in combination with paclitaxel†

    Intravenous dosage

    Adults

    AUC 5 to 7.5 IV on day 1 in combination with paclitaxel (175 to 185 mg/m2 IV over 3 hours on day 1), every 3 weeks for 6 cycles. In clinical trials, carboplatin combined with paclitaxel has been shown to be less toxic and produce similar efficacy to cisplatin combined with paclitaxel as first-line treatment of patients with advanced ovarian cancer.[13626][40931][40932] Additionally, carboplatin AUC 6 IV on day 1 in combination with paclitaxel (80 mg/m2 IV on days 1, 8, and 15), every 3 weeks for 6 cycles has been given. This dose-dense combination was compared to conventional carboplatin/paclitaxel in 631 patients with advanced ovarian cancer. Progression-free survival, the primary endpoint, was significantly higher in the dose-dense arm (28 months vs. 17.2 months, p = 0.0015).[40935]

    for the first-line treatment of ovarian cancer in combination with docetaxel†

    Intravenous dosage

    Adults

    AUC 5 IV on day 1, immediately preceded by docetaxel (75 mg/m2 IV over 1 hour on day 1), repeated every 3 weeks for 6 cycles. In a phase III trial of 1077 patients, carboplatin combined with docetaxel was compared to carboplatin combined with paclitaxel. No significant differences in response rate, progression-free survival, or overall survival were observed between the 2 groups. Grades 2 to 4 neurosensory toxicity were significantly greater in the paclitaxel containing regimen (30% vs. 11%, p < 0.001) and grades 3 to 4 neutropenia were significantly higher in the docetaxel containing regimen (94% vs. 84%, p < 0.001).[33942]

    For treatment of non-small cell lung cancer (NSCLC)†

    for the treatment of advanced or metastatic NSCLC in combination with paclitaxel†

    Intravenous dosage

    Adults

    Carboplatin AUC 6 IV in combination with paclitaxel (200 mg/m2) IV on day 1 given every 21 days produced an overall survival of 12.3 months in a phase 3 comparison of 4 chemotherapy doublets in advanced NSCLC.[34305] In another similar 4-arm phase 3 comparison, carboplatin AUC 6 IV on day 1 in combination with paclitaxel 225 mg/m2 IV on day 1 given every 21 days, produced an overall survival of 7.8 months, which was similar to the reference regimen of cisplatin and paclitaxel.[41098]

    for first-line treatment of unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with docetaxel†

    Intravenous dosage

    Adults

    AUC 6 IV in combination with docetaxel (75 mg/m2 IV) on day 1 given every 21 days for 4 to 6 cycles. In a phase 3 trial of 1,203 patients with unresectable locally advanced or metastatic NSCLC, docetaxel and platinum combinations (cisplatin or carboplatin) were compared with cisplatin/vinorelbine. No difference was observed between docetaxel/carboplatin and cisplatin/vinorelbine in overall survival, the primary endpoint. Grade 3 and 4 anemia and nausea/vomiting were significantly lower in both docetaxel containing arms. In addition, hospitalizations and treatment discontinuation secondary to toxicity were higher with cisplatin/vinorelbine.[44411] A separate phase 3 trial conducted in 422 patients with inoperable, locally advanced or metastatic NSCLC compared docetaxel/carboplatin to mitomycin C/cisplatin plus either ifosfamide or vinblastine. The primary endpoint, 1-year overall survival, was not significantly different between the treatment arms. Grade 3 and 4 neutropenia, infection, and mucositis were all significantly higher with docetaxel/carboplatin, while quality of life scores were significantly better.[34309]

    for first-line treatment of inoperable, locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with gemcitabine†

    Intravenous dosage

    Adults

    AUC 5 IV on day 1 in combination with gemcitabine 1,200 mg/m2 IV on days 1 and 8, every 21 days for 6 cycles.[34307] Alternatively, carboplatin AUC 5 IV on day 1 with gemcitabine 1,000 mg/m2 IV on days 1, 8 and 15, repeated every 28 days for 4 cycles[34308] or, carboplatin AUC 5 IV day 1 with gemcitabine 1,000 mg/m2 IV on days 1 and 8, repeated every 21 days for 4 cycles, have also been studied.[42689]

    for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients who are not candidates for curative surgery or radiation in combination with nanoparticle albumin-bound paclitaxel†

    Intravenous dosage

    Adults

    AUC 6 IV on day 1 in combination with nanoparticle albumin-bound (nab) paclitaxel (100 mg/m2 IV over 30 minutes on days 1, 8, and 15), repeated every 21 days; administer carboplatin immediately after the nab-paclitaxel infusion on day 1.[30742] Nab-paclitaxel plus carboplatin was noninferior to paclitaxel plus carboplatin in patients with previously untreated non-resectable stage IIIB or stage IV non-small cell lung cancer (NSCLC) in a multicenter, randomized, phase 3 trial (n = 1,052). The primary endpoint of overall response rate (ORR) assessed by independent radiologic review was significantly improved with nab-paclitaxel/carboplatin compared with solvent-based (sb) paclitaxel plus carboplatin (33% vs. 25%); all responding patients in the nab-paclitaxel arm had a partial response (PR) while 1 patient in the sb-paclitaxel arm achieved a complete response. In a subgroup analysis, the ORR was significantly improved with nab-paclitaxel plus carboplatin in patients with squamous cell histology (41% vs. 24%) but not nonsquamous cell histology (26% vs. 25%). Median progression-free survival (6.3 months vs. 5.8 months) and overall survival (12.1 months vs. 11.2 months) were nonsignificantly improved with nab-paclitaxel/carboplatin.[42820]

    for the first-line treatment of stage IIIB or IV non-small cell lung cancer (NSCLC) in combination with pemetrexed†

    Intravenous dosage

    Adults

    AUC 5 IV in combination with pemetrexed (500 mg/m2 IV) on day 1, repeated every 3 weeks for 4 cycles. In a phase 3 trial, 436 patients were randomized to pemetrexed/carboplatin or gemcitabine/carboplatin. No significant differences were observed for the primary endpoint, health-related quality of life, or the secondary endpoint, overall survival. Grade 3 or 4 toxicities were significantly worse in the gemcitabine/carboplatin arm.[42689]

    for first-line treatment of metastatic, nonsquamous, NSCLC, in combination with pemetrexed and pembrolizumab†

    Intravenous dosage

    Adults

    AUC 5 IV on day 1 and pemetrexed (500 mg/m2 IV on day 1) repeated every 21 days for 4 cycles in combination with pembrolizumab (200 mg IV on day 1 every 3 weeks OR 400 mg IV on day 1 every 6 weeks). Administer pembrolizumab prior to pemetrexed and chemotherapy when given on the same day. After the initial dose, monitor the nadir ANC and platelet count to assess for possible pemetrexed dose reductions. In a multicenter double-blind clinical trial (KEYNOTE-189), patients with previously untreated metastatic, EGFR- and ALK-negative, nonsquamous NSCLC, regardless of PD-L1 status, were randomized to treatment with pemetrexed plus either cisplatin or carboplatin, in combination with either pembrolizumab (n = 410) or placebo (n = 206). After a median follow-up of 31 months, the median overall survival (22 months vs. 10.6 months), progression-free survival (9 months vs. 4.9 months), and overall response rate (48.3% vs. 19.9%) were significantly improved in the pembrolizumab arm. The median duration of response was 12.5 months for patients who received pembrolizumab plus pemetrexed/platinum chemotherapy compared with 7.1 months in those receiving placebo plus pemetrexed/platinum chemotherapy.[57889] [28376] [66703]

    for the first-line treatment of metastatic squamous non-small cell lung cancer (NSCLC), in combination with pembrolizumab and either paclitaxel or nab-paclitaxel†

    Intravenous dosage

    Adults

    AUC 6 IV on day 1 with either paclitaxel (200 mg/m2 IV on day 1) or nab-paclitaxel (100 mg/m2 IV on days 1, 8, and 15) repeated every 3 weeks for 4 cycles in combination with pembrolizumab (200 mg IV on day 1 every 3 weeks OR 400 mg IV on day 1 every 6 weeks). Administer pembrolizumab prior to chemotherapy when given on the same day. Following completion of platinum-based therapy, pembrolizumab may be continued as maintenance therapy until disease progression or unacceptable toxicity, for up to 24 months. In a multicenter, randomized, double-blind clinical trial (KEYNOTE-407), treatment with pembrolizumab plus carboplatin and either paclitaxel or nab-paclitaxel (n = 278) significantly improved median overall survival (17.2 months vs. 11.6 months) and progression-free survival (6.4 months vs. 4.8 months) compared with placebo plus carboplatin and paclitaxel/nab-paclitaxel (n = 281) in patients with metastatic squamous NSCLC. The overall response rate was also significantly improved in the pembrolizumab arm (58% vs. 35%), for a median duration of 7.2 months and 4.9 months, respectively.[57889] [66530]

    for the first-line treatment of unresectable, locally advanced, recurrent, or metastatic non-squamous non-small cell lung cancer (NSCLC) in combination with bevacizumab and paclitaxel†

    Intravenous dosage

    Adults

    AUC 6 IV on day 1, preceded by bevacizumab (15 mg/kg IV over 90 minutes) and paclitaxel (200 mg/m2 IV over 3 hours), every 3 weeks for 6 cycles of chemotherapy. After completion of chemotherapy, continue bevacizumab (15 mg/kg IV), on day 1 of each 21-day cycle until disease progression or unacceptable toxicity. To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphenhydramine (or equivalent) 50 mg IV 30 to 60 minutes before paclitaxel, and an IV H2-blocker 30 to 60 minutes before paclitaxel. If the first bevacizumab infusion is well tolerated, the second infusion may be given over 60 minutes; if the 60-minute infusion is well tolerated, subsequent infusions may be given over 30 minutes. In a randomized, open-label clinical trial (n = 878), median overall survival was significantly longer in chemotherapy-naive patients with locally advanced, metastatic, or recurrent nonsquamous NSCLC treated with bevacizumab/paclitaxel/carboplatin (BCP) compared with paclitaxel/carboplatin (CP) alone (12.3 months vs. 10.3 months); investigator-assessed progression-free survival (PFS) was also longer in the bevacizumab arm. In an exploratory analysis, the impact of bevacizumab was not significant in women, patients age 65 years and older, or in patients with weight loss of 5% or more at study entry.[60402]

    for the first-line treatment of metastatic nonsquamous non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, in combination with atezolizumab, bevacizumab, and paclitaxel†

    Intravenous dosage

    Adults

    AUC 6 IV on day 1, every 3 weeks for a maximum of 4 to 6 cycles of chemotherapy. Administer in combination with paclitaxel (200 mg/m2 IV, or 175 mg/m2 IV in Asian patients, every 3 weeks for up to 4 to 6 cycles), bevacizumab (15 mg/kg IV until disease progression or unacceptable toxicity), and atezolizumab (840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity). Administer atezolizumab prior to bevacizumab and chemotherapy when given on the same day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, open-label, phase 3 clinical trial (IMpower150), treatment with atezolizumab plus bevacizumab/paclitaxel/carboplatin (ABCP) significantly improved overall survival in patients with metastatic nonsquamous NSCLC compared with BCP without atezolizumab (19.2 months vs. 14.7 months); overall survival with atezolizumab/paclitaxel/carboplatin was not significantly different from BCP. Progression-free survival was also significantly improved in the ABCP arm compared with BCP (8.5 months vs. 7 months). The objective response rate was 55% (complete response [CR], 4%) versus 42% (CR, 1%), respectively, for a median duration of 10.8 months and 6.5 months, respectively.[60793] [63819]

    for the first-line treatment of metastatic nonsquamous non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, in combination with nanoparticle albumin-bound (nab) paclitaxel and atezolizumab

    Intravenous dosage

    Adults

    AUC 6 IV on day 1, every 3 weeks for a maximum of 4 to 6 cycles of chemotherapy. Administer in combination with nab-paclitaxel (100 mg/m2 IV on days 1, 8, and 15) and atezolizumab (840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity). Administer atezolizumab prior to chemotherapy when given on the same day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. First-line treatment of EGFR- and ALK-negative metastatic NSCLC with atezolizumab plus nab-paclitaxel and carboplatin significantly improved median overall survival (18.6 months vs. 13.9 months) and median progression-free survival (7.2 months vs. 6.5 months) compared with nab-paclitaxel and carboplatin alone in a multicenter, randomized, open-label trial (IMpower130). The overall response rate was 46% (complete response [CR], 5%) in the atezolizumab arm compared with 32% (CR, 1%) in the control arm, for a median duration of 10.8 months versus 7.8 months, respectively.[60793] [66441]

    For treatment of head and neck cancer†

    for the treatment of advanced-stage squamous cell carcinoma of the head and neck in combination with 5-fluorouracil and radiation therapy†

    Intravenous dosage

    Adults

    70 mg/m2/day IV on days 1 through 4 in combination with 5-fluorouracil (5-FU) (600 mg/m2/day continuous IV infusion on days 1 through 4). Chemotherapy cycles were started on days 1, 22, and 43 and were administered concurrently with radiotherapy (RT). In a phase III trial, 226 patients with stage III or IV squamous cell carcinoma of the oropharynx (no evidence of distant metastasis) were randomized to receive RT alone or concomitantly with carboplatin/5-FU. Overall survival at 5 years was significantly improved in the chemoradiotherapy arm (22.4% vs. 15.8%, p = 0.05). The 5-year specific disease free survival rate (26.6% vs. 14.6%, p = 0.01) and locoregional control rate (47.6% vs. 24.7%, p = 0.002) were also significantly improved with chemoradiotherapy. Hematologic and skin toxicities were more common in chemoradiotherapy arm. In addition, grades 3 and 4 mucositis and poor nutritional status occurred more frequently with concomitant therapy. There were no significant differences in late toxic effects between the arms when assessed at 5 years.[43174][43119]

    for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck in combination with 5-fluorouracil†

    Intravenous dosage

    Adults

    300 mg/m2 IV on day 1 in combination with 5-fluorouracil (5-FU) (1,000 mg/m2/day continuous IV infusion over 96 hours on days 1 through 4); repeated every 4 weeks. In a phase III trial, 277 patients were randomized to receive carboplatin-5-FU, cisplatin-5-FU, or methotrexate (MTX). An increase in overall response rate was achieved with carboplatin-5-FU versus MTX, which was of borderline statistical significance (21% vs. 10%, p = 0.05). The overall response rate was numerically lower with carboplatin/5-FU compared to cisplatin-5-FU (21% vs. 32%).[43120]

    for the first-line treatment of recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with fluorouracil and cetuximab†

    Intravenous dosage

    Adults

    AUC 5 IV on day 1, in combination with fluorouracil (1,000 mg/m2 per day IV infusion over days 1 to 4), every 3 weeks for up to 6 cycles. Administer with cetuximab (400 mg/m2 IV as an initial loading dose on day 1 followed by weekly infusions of cetuximab 250 mg/m2 IV; alternatively, cetuximab may be administered at a dose of 500 mg/m2 IV every 2 weeks). Complete cetuximab administration 1 hour prior to chemotherapy and continue until disease progression or unacceptable toxicity. In a phase 3 trial, 442 patients were randomized to receive a platinum (cisplatin or carboplatin) and fluorouracil with or without cetuximab. Overall survival, the primary endpoint, was significantly greater with the addition of cetuximab to chemotherapy compared with chemotherapy alone (10.1 months vs. 7.4 months). However, sepsis, hypomagnesemia, grade 3 skin reactions, and grade 3 or 4 infusion reactions occurred more frequently with the addition of cetuximab.[35055]

    for the treatment of advanced squamous cell carcinoma of the head and neck in combination with paclitaxel and radiotherapy†

    Intravenous dosage

    Adults

    100 mg/m2 IV weekly in combination with paclitaxel (40 to 45 mg/m2 IV weekly). Chemotherapy was administered weekly prior to radiation therapy. In a clinical trial, 62 patients were administered carboplatin-paclitaxel concomitantly with radiation therapy. An overall survival of 33 months was achieved. A complete response (CR) occurred in 75% of patients; among patients with a CR, an overall survival of 49 months was achieved. At a follow-up of 30 months, a local control rate of 63% was observed.[43182]

    For treatment of testicular cancer†

    for the treatment of testicular cancer in combination with etoposide and bleomycin†

    Intravenous dosage

    Adults

    Carboplatin AUC 5 IV on day 1 in combination with etoposide (120 mg/m2/day IV on days 1 through 3) and bleomycin (30 international units on day 2), repeated every 21 days for 4 cycles has been used. In a randomized trial, the combination of carboplatin (AUC 5), etoposide, and bleomycin (CEB) was compared with the standard regimen of bleomycin, etoposide, and cisplatin (BEP) in patients with good-prognosis, metastatic testicular cancer. The combination containing carboplatin resulted in a significantly lower response rate than the cisplatin-containing regimen (87.3% vs. 94.4%, respectively).[25919]

    for the treatment of stage I seminoma†

    Intravenous dosage

    Adults

    Single dose carboplatin IV (AUC 7 if measured by EDTA; 90% of that dose if measured by 24-hour urinary creatinine clearance) after resection. In a phase III trial of patients with stage I seminoma, no difference in relapse-free rates were observed between single dose carboplatin and adjuvant radiotherapy amongst the 1,447 patients who met the minimum follow-up requirement of 5 years. Contralateral germ-cell tumors occurred in only 2 patients randomized to receive carboplatin as compared to 15 patients randomized to receive radiotherapy.[49358]

    For the treatment of relapsed or refractory non-Hodgkin's lymphoma (NHL)† in combination with ifosfamide and etoposide

    Intravenous dosage

    Adults

    Carboplatin AUC 5 IV on day 2 (Max: 800 mg), ifosfamide 5 g/m2 IV mixed with equal dose of mesna via continuous intravenous infusion over 24 hours beginning on day 2, and etoposide 100 mg/m2/day on days 1 through 3, every 2 weeks (ICE regimen) for 3 cycles, was developed to treated relapsed NHL and allow for adequate stem cell collection prior to transplant.[29307] Alternative dosage regimens have been used, including some in the outpatient setting.[51026]

    For stem cell transplant preparation†

    for stem cell transplant preparation, in combination with ifosfamide and etoposide, prior to autologous stem cell transplant for the treatment of relapsed or refractory germ cell tumor†

    Intravenous dosage

    Adults

    Ifosfamide 0 to 10 g/m2 IV in 4 divided doses on days -6 to -3, in combination with carboplatin 1,500 to 2,000 mg/m2 IV in 3 divided doses on days -6 to -4 (1,500 mg/m2) or in 4 divided doses on days -6 to -3 (more than 1,500 mg/m2), and etoposide 1,200 to 2,400 mg/m2 IV in 4 divided doses on days -6 to -3. Ifosfamide was administered on days -6 to -3 as a 22-hour infusion and mesna (each dose was 20% of the total dose/day of ifosfamide) was administered before the start of ifosfamide and every 6 hours after, including 2 doses after the final ifosfamide infusion. Each carboplatin dose was administered as a 1 hour infusion. Etoposide was administered undiluted through a central line.[50463]

    for stem cell mobilization in combination with ifosfamide and etoposide, in transplant eligible patients with non-Hodgkin's lymphoma

    Intravenous dosage

    Adults

    Etoposide 100 mg/m2/day IV on days 1 to 3 in combination with carboplatin AUC 5 (Max dose: 800 mg) IV on day 2 and ifosfamide 5 g/m2 mixed with an equal dose of mesna administered via continuous IV infusion for 24 hours beginning day 2. Filgrastim was administered at 10 mcg/kg/day starting on day 5 until completion of leukapheresis.[29307]

    For the treatment of malignant glioma†

    for the treatment of recurrent grade III malignant glioma in combination with teniposide†

    Intravenous dosage

    Adults

    350 mg/m2 IV on day 1 in combination with teniposide 50 mg/m2/day IV on days 1, 2, and 3, every 28 days. Treatment has been studied up to a maximum of 10 cycles.[50299]

    for the treatment of previously untreated, low-grade malignant glioma in combination with vincristine†

    Intravenous dosage

    Adolescents <= 16 years, Children, and Infants > 3 months

    175 mg/m2 IV once weekly on weeks 1 through 4 and 7 through 10 in combination with vincristine 1.5 mg/m2 IV (Max dose: 2 mg) once weekly on weeks 1 through 10 as induction therapy.[58630][50300] Begin maintenance therapy on week 12 with carboplatin 175 mg/m2 IV once weekly for 4 weeks and vincristine 1.5 mg/m2 (Max dose: 2 mg) IV once weekly for 3 weeks repeated every 6 weeks for 8 cycles. Do not start maintenance therapy or the next cycle of maintenance therapy until the ANC is more than 1,000 cells/mm3 and the platelet count is more than 100,000 cells/mm3.[58630]

    for the treatment of recurrent high-grade malignant glioma†

    Intravenous dosage

    Adults

    AUC 5 IV on day 1, every 28 days for 6 cycles.[50316] Alternately, carboplatin 350 to 400 mg/m2 IV on day 1, every 21 days for up to 8 cycles, has also been studied.[50317]

    For the first-line treatment of advanced transitional-cell bladder cancer†, in combination with paclitaxel

    Intravenous dosage

    Adults

    AUC of 6 IV over 30 minutes on day 1 following paclitaxel 225 mg/m2 IV over 3 hours repeated every 21 days (CP regimen) for 6 cycles was compared with methotrexate 30 mg/m2 on days 1, 15, and 22, vinblastine 3 mg/m2 IV on days 2, 15, and 22, doxorubicin 30 mg/m2 on day 2, and cisplatin 70 mg/m2 on day 2 (MVAC regimen) in a randomized, phase III trial. In this study, the median overall survival (OS) times were 13.8 and 15.4 months with CP and MVAC, respectively (p = 0.75) in 85 patients (median follow-up of 32.5 months). This study was halted due to slow patient accrual and was therefore underpowered to detect a difference in the primary endpoint of OS. The progression-free survival time was 5.2 months in the CP arm and 8.7 months in the MVAC arm (p = 0.24). Grade 3 or higher toxicity reported less often with CP compared with MVAC included neutropenia (29% vs. 67%), anemia (5% vs. 38%), thrombocytopenia (10% vs. 21%), fatigue (10% vs. 24%), and dyspnea (2% vs. 14%); grade 3 sensory neuropathy occurred more often with CP (15% vs. 2%). Additionally, worst degree toxicity of grade 4 or higher occurred in fewer patients in the CP arm (15% vs. 33%) and there was 1 treatment-related death in each study arm.[47217]

    For the treatment of breast cancer†

    for the neoadjuvant treatment of high-risk, early-stage hormone receptor (HR)-negative, HER2-negative (triple-negative) breast cancer, in combination with paclitaxel and pembrolizumab, followed by pembrolizumab/cyclophosphamide/doxorubicin†

    Intravenous dosage

    Adults

    AUC 5 IV on day 1 every 3 weeks for 4 cycles in combination with paclitaxel (80 mg/m2 IV once weekly for 12 weeks) and pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks); administer pembrolizumab prior to chemotherapy when given on the same day. Alternatively, carboplatin may be dosed once weekly at an AUC of 1.5 IV for 12 weeks. After completion of 12 weeks (4 cycles) of pembrolizumab, paclitaxel, and carboplatin, continue neoadjuvant therapy with 4 cycles of doxorubicin (60 mg/m2 IV every 3 weeks) plus cyclophosphamide (600 mg/m2 IV every 3 weeks) and pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks), followed by surgery; administer pembrolizumab prior to chemotherapy when given on the same day. After surgery, administer pembrolizumab 200 mg IV every 3 weeks for up to 9 doses OR 400 mg IV every 6 weeks for up to 5 doses or until disease progression or unacceptable toxicity. Do not administer adjuvant pembrolizumab monotherapy to patients with disease progression or unacceptable toxicity related to neoadjuvant treatment with pembrolizumab plus chemotherapy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with high-risk (tumor size more than 1 cm but up to and including 2 cm in diameter with nodal involvement; or tumor size more than 2 cm in diameter regardless of nodal involvement), early stage triple-negative breast cancer were randomized to neoadjuvant treatment with pembrolizumab or placebo in combination with carboplatin and paclitaxel, followed by anthracycline and cyclophosphamide in a phase 3 clinical trial (KEYNOTE-522); after definitive surgery, patients received adjuvant pembrolizumab or placebo. Treatment with pembrolizumab plus chemotherapy significantly improved the rate of pathologic complete response (pCR) (63% vs. 55.6%) compared with placebo plus chemotherapy. The median event-free survival (EFS) was not reached in either arm, although EFS at 18 months was 91.3% in patients who received pembrolizumab compared with 85.3% in those who received placebo (HR 0.63; 95% CI, 0.43 to 0.93); overall survival results are immature.[66036] [57889]

    for the neoadjuvant treatment of high-risk, early-stage hormone receptor (HR)-negative, HER2-negative (triple-negative) breast cancer, in combination with paclitaxel and pembrolizumab, followed by pembrolizumab/cyclophosphamide/epirubicin†

    Intravenous dosage

    Adults

    AUC 5 IV on day 1 every 3 weeks for 4 cycles in combination with paclitaxel (80 mg/m2 IV once weekly for 12 weeks) and pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks); administer pembrolizumab prior to chemotherapy when given on the same day. Alternatively, carboplatin may be dosed once weekly at an AUC of 1.5 IV for 12 weeks. After completion of 12 weeks (4 cycles) of pembrolizumab, paclitaxel, and carboplatin, continue neoadjuvant therapy with 4 cycles of epirubicin (90 mg/m2 IV every 3 weeks) plus cyclophosphamide (600 mg/m2 IV every 3 weeks) and pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks), followed by surgery; administer pembrolizumab prior to chemotherapy when given on the same day. After surgery, administer pembrolizumab 200 mg IV every 3 weeks for up to 9 doses OR 400 mg IV every 6 weeks for up to 5 doses or until disease progression or unacceptable toxicity. Do not administer adjuvant pembrolizumab monotherapy to patients with disease progression or unacceptable toxicity related to neoadjuvant treatment with pembrolizumab plus chemotherapy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with high-risk (tumor size more than 1 cm but up to and including 2 cm in diameter with nodal involvement; or tumor size more than 2 cm in diameter regardless of nodal involvement), early stage triple-negative breast cancer were randomized to neoadjuvant treatment with pembrolizumab or placebo in combination with carboplatin and paclitaxel, followed by anthracycline and cyclophosphamide in a phase 3 clinical trial (KEYNOTE-522); after definitive surgery, patients received adjuvant pembrolizumab or placebo. Treatment with pembrolizumab plus chemotherapy significantly improved the rate of pathologic complete response (pCR) (63% vs. 55.6%) compared with placebo plus chemotherapy. The median event-free survival (EFS) was not reached in either arm, although EFS at 18 months was 91.3% in patients who received pembrolizumab compared with 85.3% in those who received placebo (HR 0.63; 95% CI, 0.43 to 0.93); overall survival results are immature.[66036]

    for adjuvant treatment of patients with HER2 overexpressing node-positive or high-risk node negative breast cancer†, in combination with docetaxel and trastuzumab

    Intravenous dosage

    Adults

    Carboplatin AUC 6 IV with docetaxel (75 mg/m2 IV) on day 1 repeated every 3 weeks for a total of 6 cycles plus trastuzumab (8 mg/kg IV infusion on week 1, followed by 6 mg/kg IV infusion every 3 weeks for a total of 52 weeks) (TCH regimen). Interim analysis of a phase 3 trial comparing the TCH regimen versus doxorubicin, cyclophosphamide, docetaxel, and trastuzumab showed similar efficacy. The incidence of cardiac toxicity is significantly less with TCH.[33126]

    for the first-line treatment of metastatic breast cancer in combination with paclitaxel†

    Intravenous dosage

    Adults

    Carboplatin AUC 6 IV on day 1 in combination with paclitaxel 175 mg/m2 IV over 3 hours on day 1, every 3 weeks for 6 cycles has been studied.[50012] [50011]

    for the front-line treatment of HER2-overexpressing metastatic breast cancer† in combination with paclitaxel and trastuzumab

    Intravenous dosage

    Adults

    AUC 6 IV in combination with paclitaxel 175 mg/m2 IV beginning in week 1 repeated every 3 weeks for 6 cycles. Alternatively, carboplatin AUC 2 IV and paclitaxel 80 mg/m2 IV may be administered weekly for 3 weeks with a 1 week rest to complete 6 4-week cycles. Give both regimens with trastuzumab (4 mg/kg IV on week 1 then 2 mg/kg IV once/week starting week 2), continue trastuzumab until disease progression or unacceptable toxicity. A phase 3 trial of 196 patients with previously untreated HER2-overexpressing metastatic breast cancer examined trastuzumab and paclitaxel +/- carboplatin. The primary endpoint, overall response rate, was significantly increased with the addition of carboplatin (52% vs. 36%). Progression-free survival was also significantly better in the carboplatin arm (10.7 months vs. 7.1 months). Grade 4 neutropenia (36% vs. 12%) and grade 3 thrombocytopenia (9% vs. 1%) occurred more frequently in the carboplatin arm.[34295] A comparison of 2 parallel phase 2 studies revealed an increase in overall response rate, median time to disease progression, and overall survival with weekly administration of carboplatin/paclitaxel versus every 3 week administration.[34296]

    for the treatment of locally recurrent unresectable or metastatic, PD-L1 positive (CPS 10 or more), triple negative breast cancer (TNBC), in combination with gemcitabine and pembrolizumab†

    Intravenous dosage

    Adults

    AUC 2 IV on days 1 and 8, every 21 days in combination with gemcitabine (1,000 mg/m2 IV on days 1 and 8, every 21 days) and pembrolizumab (200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression); the number of cycles of gemcitabine plus carboplatin was not specified.[66122] [66123] [57889] Administer pembrolizumab prior to chemotherapy when given on the same day. In a multicenter, double-blind clinical trial (KEYNOTE-355), patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting were randomized to treatment with either pembrolizumab or placebo in combination with paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin regardless of tumor PD-L1 expression. The addition of pembrolizumab to chemotherapy significantly improved the median progression-free survival (9.7 months vs. 5.6 months) compared with placebo plus chemotherapy in the subgroup of patients with a CPS of 10 or more. The objective response rate was 53% compared with 40%, respectively (complete response, 17% vs. 13%) for a median duration of 19.3 months in the pembrolizumab arm and 7.3 months in the placebo arm.[57889] [66123]

    For the treatment of relapsed or refractory acute lymphocytic leukemia (ALL) in combination with ifosfamide, etoposide, and rituximab†

    Intravenous dosage

    Adults 21 years or younger, Adolescents, and Children

    Carboplatin 635 mg/m2 IV on day 3 in combination with ifosfamide 3,000 mg/m2/day IV on days 3, 4, 5 (each dose mixed with mesna 600 mg/m2 IV, followed by mesna 600 mg/m2 IV over 15 minutes at 3, 6, 9, and 12 hours after the start of ifosfamide) and etoposide 100 mg/m2/day IV on days 3, 4, 5, repeated each cycle. Rituximab 375 mg/m2 IV was given on days 1 and 3 of cycles 1 and 2, and on day 3 only of cycle 3. Treatment was given up to a maximum of 3 cycles. Colony-stimulating factors were initiated on day 6 of each cycle and intrathecal chemotherapy was also given as appropriate. Overall response rate was 60% and overall survival at 2 to 3 years was 37.5%.[44193]

    For the treatment of poor-risk relapsed Wilms' tumor in combination with etoposide and ifosfamide†

    Intravenous dosage

    Adults <= 21 years, Adolescents, and Children

    Ifosfamide 1,800 mg/m2/day IV for 5 days (on days 0, 1, 2, 3, 4), carboplatin 400 mg/m2/day IV for 2 days (on day 0, 1) and etoposide 100 mg/m2/day IV for 5 days (on days 0, 1, 2, 3, 4), repeated every 21 days.[50019]

    For the treatment of intermediate-risk neuroblastoma in combination with etoposide, cyclophosphamide, and doxorubicin†

    Intravenous dosage

    Infants and Children

    Carboplatin has been given in combination with etoposide, cyclophosphamide, and doxorubicin, in the following fashion. In Cycles 1 and 7: Carboplatin 560 mg/m2 IV on day 1 (18 mg/kg/day in children less than 12 kg) plus etoposide 120 mg/m2/day IV on days 1, 2, 3 (4 mg/kg/day in children less than 12 kg). Cycles 2 and 6: Carboplatin 560 mg/m2 IV on day 1 (18 mg/kg/day in children less than 12 kg) plus cyclophosphamide 1,000 mg/m2 IV on day 1 (33 mg/kg/day in children less than 12 kg), and doxorubicin 30 mg/m2 IV on day 1 (1 mg/kg/day in children less than 12 kg). Cycles 3 and 5: Cyclophosphamide 1,000 mg/m2 IV on day 1 (33 mg/kg/day in children less than 12 kg) plus etoposide 120 mg/m2/day IV on days 1, 2, 3 (4 mg/kg/day in children less than 12 kg). Cycle 4: Carboplatin 560 mg/m2 IV on day 1 (18 mg/kg/day in children less than 12 kg) plus etoposide 120 mg/m2/day IV on days 1, 2, 3 (4 mg/kg/day in children less than 12 kg), and doxorubicin 30 mg/m2 IV on day 1 (1 mg/kg/day in children less than 12 kg). Cycle 8: Cyclophosphamide 1,000 mg/m2 IV on day 1 (33 mg/kg/day in children less than 12 kg) plus doxorubicin 30 mg/m2 IV on day 1 (1 mg/kg/day in children less than 12 kg). All cycles given at 3 week intervals. Patients with favorable biologic features received 4 cycles; if incomplete response after 4 cycles, patients given an additional 4 cycles. Patients with unfavorable biologic features received 8 cycles. Infants younger than 60 days of age received granulocyte colony-stimulating factor after each cycle.[49848]

    For the first-line treatment of unresectable, advanced thymoma†, in combination with paclitaxel

    Intravenous dosage

    Adults

    AUC of 6 IV over 30 minutes following paclitaxel 225 mg/m2 IV over 3 hours on day 1 repeated every 21 days for up to 6 cycles resulted in an objective response rate (ORR) of 42.9% (complete response rate, 14.3%; median duration of response, 16.9 months) in 21 patients with invasive, recurrent, or metastatic thymoma in a multicenter, phase II study. This ORR was less than the prespecified ORR of 60% that would warrant further study of this regimen. At a median follow-up of 59.4 months, the median progression-free survival time was 16.7 months and the median overall survival time was not reached. Serious toxicity reported in this study included grade 4 neutropenia and grade 3 sensory neuropathy.[47361]

    For the first-line treatment of unresectable, advanced thymic carcinoma†, in combination with paclitaxel

    Intravenous dosage

    Adults

    AUC of 6 IV over 30 minutes following paclitaxel 225 mg/m2 IV over 3 hours on day 1 administered every 21 days for up to 6 cycles resulted in an objective response rate (ORR) of 21.7% (all partial responses; median duration of response, 4.5 months) in 23 patients with invasive, recurrent, or metastatic thymic carcinoma in a multicenter, phase II study. This ORR was less than the prespecified ORR of 45% that would warrant further study of this regimen. At a median follow-up of 63.8 months, the median progression-free survival and overall survival times were 5 and 20 months, respectively. Serious toxicity reported in this study included grade 4 neutropenia and grade 3 sensory neuropathy.[47361]

    For the treatment of small cell lung cancer (SCLC)†

    for the treatment of limited-stage SCLC, in combination with etoposide and radiation therapy†

    Intravenous dosage

    Adults

    AUC 6 IV on day 1 in combination with etoposide 100 mg/m2/day IV on days 1, 2, 3, every 3 weeks for 6 courses. Hyperfractionated thoracic radiation therapy should be given concurrently with chemotherapy.[50248]

    for the first-line treatment of extensive-stage SCLC, in combination with etoposide and atezolizumab†

    Intravenous dosage

    Adults

    AUC 5 IV on day 1, every 3 weeks for 4 cycles. Administer in combination with etoposide (100 mg/m2 IV on days 1, 2, and 3, every 3 weeks for 4 cycles) and atezolizumab (840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks). Administer atezolizumab prior to chemotherapy when given on the same day. In a randomized, double-blind, phase 3 clinical trial (IMpower133), the addition of atezolizumab to carboplatin plus etoposide significantly improved overall survival (12.3 months vs. 10.3 months) and progression-free survival (5.2 months vs. 4.3 months) compared with placebo plus carboplatin/etoposide. Survival at 1 year was 51.7% versus 38.2%, respectively. Treatment was well-tolerated, with 56.5% of patients in the atezolizumab arm experiencing grade 3 or 4 adverse reactions compared with 56.1% of those in the placebo arm. Immune-related adverse reactions occurred in 39.9% versus 24.5% of patients, respectively.[63611] [60793]

    for the first-line treatment of extensive-stage SCLC, in combination with etoposide and durvalumab

    Intravenous dosage

    Adults weighing more than 30 kg

    AUC 5 to 6 IV on day 1 plus etoposide (80 to 100 mg/m2 IV on days 1 to 3), following administration of durvalumab (1,500 mg IV over 60 minutes on day 1), every 3 weeks for 4 cycles; administer durvalumab prior to chemotherapy when given on the same day. After completion of 4 cycles of durvalumab plus chemotherapy, continue durvalumab 1,500 mg IV every 4 weeks as a single agent until disease progression or unacceptable toxicity. Durvalumab significantly improved overall survival by approximately 3 months when added to platinum-etoposide chemotherapy compared with platinum-etoposide alone in patients with extensive-stage SCLC in a randomized clinical trial.[64736] [61913]

    Adults weighing 30 kg or less

    AUC 5 to 6 IV on day 1 plus etoposide (80 to 100 mg/m2 IV on days 1 to 3), following administration of durvalumab (20 mg/kg IV over 60 minutes on day 1), every 3 weeks for 4 cycles; administer durvalumab prior to chemotherapy when given on the same day. After completion of 4 cycles of durvalumab plus chemotherapy, continue durvalumab 20 mg/kg IV every 4 weeks as a single agent until disease progression or unacceptable toxicity. Durvalumab significantly improved overall survival by approximately 3 months when added to platinum-etoposide chemotherapy compared with platinum-etoposide alone in patients with extensive-stage SCLC in a randomized clinical trial.[64736] [61913]

    for the treatment of extensive-stage SCLC, in combination with etoposide†

    Intravenous dosage

    Adults

    AUC 5 IV on day 1 in combination with etoposide 80 mg/m2/day IV on days 1, 2, 3 per cycle every 3 to 4 weeks up to 4 courses.[50232]

    for the treatment of relapsed SCLC in combination with paclitaxel†

    Intravenous dosage

    Adults

    AUC 7 IV on day 1 in combination with paclitaxel 175 mg/m2 IV on day 1, every 3 weeks for 5 cycles.[25767]

    For the treatment of glioblastoma multiforme† after failing prior bevacizumab-based therapy, in combination with irinotecan and bevacizumab

    Intravenous dosage

    Adults

    AUC 4 IV on day 1 in combination with irinotecan (enzyme-inducing antiepileptic drug: 340 mg/m2 IV on days 1 and 15; non-enzyme-inducing antiepileptic drug: 125 mg/m2 IV on days 1 and 15) and bevacizumab 10 mg/kg IV on days 1 and 15, every 28 days for up to 12 cycles.[50297]

    For the treatment of previously untreated, advanced, unresectable pleural malignant mesothelioma, in combination with pemetrexed†

    Intravenous dosage

    Adults

    AUC 5 IV over 30 minutes on day 1; 30 minutes prior to carboplatin infusion on day 1, administer pemetrexed 500 mg/m2 IV over 10 minutes. Repeat every 21 days for up to 6 cycles, until disease progression or unacceptable toxicity. Premedicate pemetrexed with dexamethasone 4 mg by mouth twice daily for 3 days, beginning the day before pemetrexed administration to reduce cutaneous reactions. Additionally, supplement with folic acid (400 to 1,000 mcg by mouth daily) and vitamin B12 (1 mg IM every 3 months) beginning 7 days prior to the first dose of pemetrexed and continuing for 21 days after the last dose to reduce the severity and frequency of hematologic and GI toxicities; after the first dose, vitamin B12 may be given on the same day as pemetrexed. Do not substitute oral for IM vitamin B12.[59790] [60907] [20638] [60908] [60909]

    For the treatment of urothelial carcinoma†

    for the first-line treatment of locally advanced or metastatic urothelial carcinoma, in combination with gemcitabine and atezolizumab†

    Intravenous dosage

    Adults

    AUC 4.5 IV on day 1, in combination with gemcitabine (1,000 mg/m2 IV on days 1 and 8) and atezolizumab (1,200 mg IV over 60 minutes on day 1), every 21 days for up to 6 cycles. In a randomized phase 3 trial (the IMvigor 130 trial), the addition of atezolizumab to platinum-based chemotherapy in patients with metastatic urothelial cancer significantly improved progression-free survival (PFS) compared with platinum-based chemotherapy alone in the intent-to-treat population; the PFS benefit in the atezolizumab arm was seen across all subgroups, although it was not statistically significant in several including patients with PD-L1 0/1 expression and in patients receiving carboplatin- versus cisplatin-based regimens. At an interim analysis after 11.8 months of follow-up, overall survival was not significantly different between groups.[65902]

    for the adjuvant treatment of locally advanced urothelial cancer of the upper urinary tract (UTUC), in combination with gemcitabine†

    Intravenous dosage

    Adults

    AUC 4.5 or 5 IV over 1 hour on day 1, in combination with gemcitabine (1,000 mg/m2 IV over 30 minutes on day 1 and 8), every 21 days for 4 cycles. In a randomized, phase 3 clinical trial, treatment with gemcitabine plus either cisplatin or carboplatin significantly improved disease-free survival in patients with locally advanced UTUC when initiated within 90 days after radical nephroureterectomy compared with surveillance. Based on recommendations from the independent data monitoring committee, study enrollment was ended early and patients still within the 90-day window from nephroureterectomy were offered chemotherapy.[66092]

    For the treatment of endometrial cancer†

    for the treatment of mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer, in combination with dostarlimab and paclitaxel following by single-agent dostarlimab therapy†

    Intravenous dosage

    Adults

    AUC 5 on day 1 plus dostarlimab 500 mg IV on day 1 and paclitaxel 175 mg/m2 on day 1 repeated every 3 weeks for 6 doses; administer dostarlimab prior to chemotherapy on day 1 of each cycle. Starting 3 weeks after the sixth dose, give single-agent dostarlimab 1,000 mg IV every 6 weeks until disease progression or for up to 3 years.[66619] At a median follow-up time of approximately 25 months, the 24-month investigator-assessed progression-free survival rates were significantly higher the dostarlimab plus carboplatin and paclitaxel arm compared with the placebo plus carboplatin and paclitaxel arm in patients with primary advanced or recurrent endometrial cancer in the overall study population (36.1% vs. 18.1%) and in a subpopulation of 118 patients with dMMR/MSI-H tumors (61.4% vs. 15.7%) in a randomized, double-blind, phase 3 (RUBY) trial. At the time of this interim analysis, the 24-month overall survival rates were also significantly improved in patients who received dostarlimab compared with placebo in the overall (71.3% vs. 56%) and dMMR/MSI-H subgroup (83.3% vs. 58.7%) populations. In the overall population, 54.7% of patients had endometrioid carcinoma-type endometrial cancer, 47.8% of patients had recurrent disease, and 82.6% had not received external pelvic radiation.[69254]

    for the treatment of mismatch repair deficient (dMMR) primary advanced or recurrent endometrial cancer, in combination with paclitaxel and durvalumab†

    Intravenous dosage

    Adults

    AUC 5 or 6 IV on day 1 in combination with paclitaxel 175 mg/m2 IV on day 1 and durvalumab 1,120 mg (if patient weighs 30 kg or more) or 15 mg/kg (if patient weighs less than 30 kg) IV on day 1 and every 21 days for 6 cycles. Administer durvalumab prior to chemotherapy when given on the same day. After completion of 6 cycles of durvalumab plus chemotherapy, continue durvalumab 1,500 mg (if patient weighs 30 kg or more) or 20 mg/kg (if patient weighs less than 30 kg) IV every 4 weeks as a single agent until disease progression or unacceptable toxicity. Patients with advanced or recurrent endometrial cancer were randomized to treatment with durvalumab or placebo plus carboplatin/paclitaxel in a multicenter, randomized, double-blind clinical trial (DUO-E); enrolled patients were required to have known mismatch repair gene status. The primary outcome of progression-free survival (PFS) was significantly improved in the durvalumab arm compared with placebo in the intent-to-treat population (10.2 months vs. 9.6 months); however, based on an exploratory analysis by MMR status (not reached vs. 7 months), the PFS improvement in the overall population was primarily attributed to patients with dMMR tumors.[70771] [61913]

    for the treatment of primary advanced or recurrent endometrial cancer, in combination with paclitaxel and pembrolizumab†

    Intravenous dosage

    Adults

    AUC 5 IV and paclitaxel 175 mg/m2 IV on day 1 every 3 weeks for 6 cycles, in combination with pembrolizumab 200 mg IV every 3 weeks OR 400 mg IV every 6 weeks until disease progression or for up to 24 months in patients without disease progression. Administer pembrolizumab prior to chemotherapy when given on the same day. Treatment with pembrolizumab plus carboplatin and paclitaxel significantly improved progression-free survival (PFS) in patients with advanced or recurrent endometrial cancer compared with placebo plus carboplatin and paclitaxel in a multicenter, randomized, double-blind clinical trial (KEYNOTE-868) in both the mismatch repair deficient (dMMR) (not reached vs. 6.5 months) and mismatch repair proficient (pMMR) (11.1 months vs. 8.5 months) cohorts.[57889] [70798]

    Therapeutic Drug Monitoring

    Dosage adjustments based on hematologic parameters (based on trials of patients with ovarian cancer treated with carboplatin alone or in combination):

     

    Neutrophils

    • Nadir greater than 2,000 cells/mm3: May increase dose to 125% of the previous dose.
    • Nadir 500 cells/mm3 to 2,000 cells/mm3: No dose adjustment.
    • Nadir less than 500 cells/mm3: Reduce the dose to 75% of the previous dose.[46283]

     

    Platelets

    • Nadir greater than 100,000 cells/mm3: May increase dose to 125% of the previous dose.
    • Nadir 50,000 to 100,000 cells/mm3: No dose adjustment.
    • Nadir less than 50,000 cells/mm3: Reduce the dose to 75% of the previous dose.[46283]

    Maximum Dosage Limits

    • Adults

      Maximum dosage information is not available. For doses calculated using the Calvert formula with an estimated GFR, it is recommended to use a maximum GFR = 125 mL/min in the calculation.[29203] [42067]

    • Geriatric

      Maximum dosage information is not available. For doses calculated using the Calvert formula with an estimated GFR, it is recommended to use a maximum GFR = 125 mL/min in the calculation.[29203] [42067]

    • Adolescents

      Safety and efficacy have not been established. Maximum dosage information is not available. For doses calculated using the Calvert formula with an estimated GFR, it is recommended to use a maximum GFR = 125 mL/min in the calculation.[29203] [42067]

    • Children

      Safety and efficacy have not been established. Maximum dosage information is not available. For doses calculated using the Calvert formula with an estimated GFR, it is recommended to use a maximum GFR = 125 mL/min in the calculation.[29203] [42067]

    • Infants

      Safety and efficacy have not been established. Maximum dosage information is not available. For doses calculated using the Calvert formula with an estimated GFR, it is recommended to use a maximum GFR = 125 mL/min in the calculation.[29203] [42067]

    • Neonates

      Safety and efficacy have not been established. Maximum dosage information is not available. For doses calculated using the Calvert formula with an estimated GFR, it is recommended to use a maximum GFR = 125 mL/min in the calculation.[29203] [42067]

    Patients with Hepatic Impairment Dosing

    No dosage adjustments are needed in patients with hepatic impairment.

    Patients with Renal Impairment Dosing

    NOTE: Recommendations are only available for the initial course of treatment for ovarian cancer with carboplatin as a single agent or with cyclophosphamide. Subsequent adjustments should be done base on the toxicity of the previous course.

    CrCl >= 60 ml/min: no dosage adjustment needed.

    CrCl 41—59 ml/min: give 250 mg/m2 on day 1 of the initial course for ovarian cancer.

    CrCl 16—40 ml/min: give 200 mg/m2 on day 1 of the initial course for ovarian cancer.

    CrCl <= 15 ml/min: Data too limited to permit a recommendation.

     

    Intermittent hemodialysis

    Multiple reports document the use of carboplatin in patients who are receiving concurrent hemodialysis. Most of the reports indicate that carboplatin is removed by hemodialysis. Studies indicate that anuric patients may receive carboplatin at initial doses not exceeding 150 mg/m2 IV followed by dialysis within 24—48 hours of treatment (written communication, Bristol-Myers Squibb Oncology/Immunology Division, September 1999).

    † Off-label indication
    Revision Date: 09/11/2024, 01:56:00 AM

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Cancer 2003;98:542-53.34309 - Booton R, Lorigan P, Anderson H, et al. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol 2006;17:1111-19.35055 - Vermorken J, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-27.40931 - Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2003;21:3194-3200.40932 - du Bois A, Luck HJ, Meier W, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 2003;95:1320-1330.40935 - Katsumata N, Yasuda M, Takahashi F, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 2009;374:1331-1338.41098 - Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346:92-842067 - Food and Drug Administration (US FDA) News Release. Carboplatin dosing. Available on the World Wide Web at: https://wayback.archive-it.org/7993/20170113081146/http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm228974.htm. Accessed May 2, 2018.42689 - Gronberg BH, Bremnes RM, Flotten O, et al. Phase III study by the Norwegian Lung Cancer Study Group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small cell lung cancer. J Clin Oncol 2009;27:3217-3224.42820 - Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 2012;30(17):2055-2062.43119 - Denis F, Garaud P, Bardet E, et al. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 2004;22(1):69-7643120 - Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol 1992;10(8):1245-51.43174 - Calais G, Alfonsi M, Bardet E, et al. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 1999;91:2081-2086.43182 - Suntharalingam M, Haas ML, Conley BA, et al. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiation Oncology Biol Phys 2000;47:49-56.44193 - Griffin TC, Weitzman S, Weinstein H, Chang M, et al; Children's Oncology Group. A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD20+) non-Hodgkin's lymphoma and mature B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Pediat Blood Cancer. 2009;52(2):177-181.44411 - Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003;21:3016-302446283 - Carboplatin package insert. Bedford, OH: Bedford Laboratories;2009 Oct.47217 - Dreicer R, Manola J, Roth BJ, et al. Phase III trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium. Cancer 2004;100(8):1639-1645.47361 - Lemma GL, Lee JW, Aisner SC, et al. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol 2011;29(15):2060-2065.49358 - Oliver RT, Mead GM, Rustin GJ, et al. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol. 2011;29:957-6249848 - Baker DL, Schmidt ML, Cohn SL, et al. Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Eng J Med 2010;363:1313-1323.50011 - Fountzilas G, Dafni U, Dimopoulos MA, et al. A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer. Breast Cancer Res Treat 2009;115:87-99.50012 - Fountzilas G, Kalofonos HP, Dafni U, et al. Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 2004;15:1517-1526.50019 - Abu-Ghosh AM, Krailo MD, Goldman SC, et al. Ifosfamide, carboplatin and etoposide in children with poor-risk relapsed Wilms' tumor: a Children's Cancer Group report. Ann Oncol 2002;13:460-469.50232 - Okamoto H, Watanabe K, Kunikane H et al. Randomized phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer 2007;97:162-16950248 - Skarlos DV, Samantas E, Briassoulis E et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol 2001;123:1231-1238.50297 - Reardon DA, Desjardins A, Peters KB, et al. Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. Cancer 2011;117:5351–8.50299 - Brandes AA, Basso U, Vastola F, et al. Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol 2003;14:1727-173150300 - Packer RJ, Ater J, Allen J, et al. Carboplatin and vincristine chemotherapy for children with newly-diagnosed progressive low-grade gliomas. J Neurosurg 1997;86:747–54.50316 - Murray LJ, Bridgewater CH, Levy D. Carboplatin chemotherapy in patients with recurrent high-grade glioma. Clin Oncol 2011;23:55-6150317 - Warnick RE, Prados MD, Mack EE, Chandler KL, Doz F, Rabbitt JE, Malec MK. A phase II study of intravenous carboplatin for the treatment of recurrent gliomas. J Neurooncol 1994;19:69–74.50463 - Siegert W, Beyer J, Strohscheer I et al. High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The Germ Testicular Cancer Cooperative Study Group. J Clin Oncol 1994;12:1223-123151026 - Hertzberg MS, Crombie C, Benson W, et al. Outpatient fractionated ifosfamide, carboplatin and etoposide as salvage therapy in relapsed and refractory non-Hodgkin’s and Hodgkin’s lymphoma. Annals of Oncology 2006;17 (Suppl 4):iv25-iv30.51181 - Erbitux (cetuximab) injection package insert. Branchburg, NJ:ImClone LLC;2021 Sept.57889 - Keytruda (pembrolizumab) injection package insert. Whitehouse Station, NJ: Merck Sharp and Dohme Corp.; 2024 Sept.58630 - Ater JL, Zhou T, Holmes E, et al. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol 2012;30(21):2641-2647.59790 - Alimta (pemetrexed) injection package insert. Indianapolis, IN: Lilly USA, LLC; 2015 Feb.60402 - Avastin (bevacizumab) IV package insert. South San Francisco, CA: Genentech, Inc.; 2022 Sept.60793 - Tecentriq (atezolizumab) injection package insert. South San Francisco, CA: Genentech, Inc.; 2024 Apr.60907 - Santoro A, O’Brien ME, Stahel RA, et al. Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaive patients with malignant pleural mesothelioma: results of the international expanded access program. Journal of Thoracic Oncology. 2008;3(7):756-763.60908 - Castagneto B, Botta M, Aitini E, et al. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Annals of Oncology. 2008;19:370-373.60909 - Katirtzoglou N, Gkiozos I, Makrilia N, et al. Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study. Clinical Lung Cancer. 2010;11(1)30-35.61913 - Imfinzi (durvalumab) injection package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024 Aug.63611 - Horn L, Mansfield AS, Szczesna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. NEJM. 2018;379:2220-2229.63819 - Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic non-squamous NSCLC. NEJM. 2018;378(24):2288-2301.64736 - Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. The Lancet. 2019;394:1929-1939.65902 - Galsky MD, Arija JAA, Bamias A, et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicenter, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395:1547-1557.66036 - Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. NEJM. 2020;382(9):810-821.66092 - Birtle A, Johnson M, Chester J, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet. 2020;395:1268-1277.66122 - Cortes Castan J, Guo Z, Karantza V, et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated, locally recurrent, inoperable or metastatic triple-negative breast cancer (mTNBC). Annals of Oncology. 2017;28(10):x25.66123 - Cortes J, Cescon DW, Rugo HS, et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. Journal of Clinical Oncology. 2020;38(15_suppl):1000.66441 - West H, McCleod M, Hussein M, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:924-937.66530 - Paz-Ares L, Vicente D, Tafreshi A, et al. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. Journal of Thoracic Oncology. 2020;15(10):1657-1669.66619 - Jemperli (dostarlimab-gxly) injection package insert. Research Triangle Park, NC: Glaxo Smith Kline LLC; 2024 Aug.66703 - Rodriguez-Abreu1 D, Powell SF, Hochmair MJ, et al. Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Annals of Oncology. 2021. Epub ahead of print, doi: 10.1016/j.annonc.2021.04.00869254 - Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med 2023;388(23):2145-2158.70771 - Westin SN, Moore K, Chon HS, et al. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2023;42(3):283-299.70798 - Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Eng J Med. 2023;388(23):2159-2170.

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    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (10139-0060) (GeneraMedix Pharmaceuticals Inc.) (off market)

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (61703-0339) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (61703-0339) (Hospira Worldwide, Inc., a Pfizer Company) null

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (50742-0445) (Ingenus Pharmaceuticals, LLC) null

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (71288-0100) (Meitheal Pharmaceuticals, Inc.) (off market)

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (67457-0491) (Mylan Institutional LLC ) (off market)

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (25021-0202) (Sagent Pharmaceuticals) (off market)

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (66758-0047) (Sandoz Inc. a Novartis Company) (off market)

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (47335-0150) (Sun Pharmaceutical Industries, Inc.) null

    Carboplatin Solution for injection

    Carboplatin 50mg/5ml Solution for Injection (Amerinet) (55390-0220) (Bedford Laboratories, a Hikma Company) (off market)

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (Amerinet) (61703-0339) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (NOVAPLUS) (61703-0360) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

    Carboplatin Solution for injection

    Carboplatin 50mg/5mL Solution for Injection (NOVAPLUS) (61703-0360) (Hospira Worldwide, Inc., a Pfizer Company) null

    Carboplatin Solution for injection

    Carboplatin 50mg/5ml Solution for Injection (PREMIER ProRx) (00703-4244) (Teva Pharmaceuticals USA) nullCarboplatin 50mg/5ml Solution for Injection (PREMIER ProRx) package photo

    Carboplatin Solution for injection

    Carboplatin 600mg/60ml Solution for Injection (55390-0156) (Bedford Laboratories, a Hikma Company) (off market)

    Carboplatin Solution for injection

    Carboplatin 600mg/60ml Solution for Injection (63323-0172) (Fresenius Kabi AG) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60ml Solution for Injection (25021-0202) (Sagent Pharmaceuticals) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60ml Solution for Injection (66758-0047) (Sandoz Inc. a Novartis Company) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60ml Solution for Injection (00703-3249) (Teva Pharmaceuticals USA) (off market)

    Carboplatin Solution for injection

    Carboplatin 600mg/60ml Solution for Injection (00703-4239) (Teva Pharmaceuticals USA) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60ml Solution for Injection (00591-3454) (Teva/Actavis US) (off market)

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (16729-0295) (Accord Healthcare, Inc.) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (47781-0606) (Alvogen, Inc.) (off market)

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (60505-6282) (Apotex Corp) nullCarboplatin 600mg/60mL Solution for Injection package photo

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (54288-0167) (BPI Labs, LLC) nullCarboplatin 600mg/60mL Solution for Injection package photo

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (55150-0386) (Eugia US LLC fka AuroMedics Pharma LLC) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (61703-0339) (Hospira Worldwide, Inc., a Pfizer Company) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (50742-0448) (Ingenus Pharmaceuticals, LLC) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (71288-0100) (Meitheal Pharmaceuticals, Inc.) (off market)

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (67457-0494) (Mylan Institutional LLC ) (off market)

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (47335-0284) (Sun Pharmaceutical Industries, Inc.) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (NOVAPLUS) (61703-0600) (Hospira Worldwide, Inc., a Pfizer Company) null

    Carboplatin Solution for injection

    Carboplatin 600mg/60mL Solution for Injection (PREMIER ProRx) (00703-4239) (Teva Pharmaceuticals USA) null

    Carboplatin Solution for injection

    Paraplatin 1000mg/100mL Solution for Injection (69448-0005) (Accord BioPharma a division of Accord Healthcare, Inc.) null

    Carboplatin Solution for injection

    Paraplatin 150mg/15ml Solution for Injection (00015-3211) (Bristol Myers Squibb Oncology Products) (off market)

    Carboplatin Solution for injection

    Paraplatin 150mg/15mL Solution for Injection (69448-0005) (Accord BioPharma a division of Accord Healthcare, Inc.) null

    Carboplatin Solution for injection

    Paraplatin 450mg/45ml Solution for Injection (00015-3212) (Bristol Myers Squibb Oncology Products) (off market)

    Carboplatin Solution for injection

    Paraplatin 450mg/45mL Solution for Injection (69448-0005) (Accord BioPharma a division of Accord Healthcare, Inc.) null

    Carboplatin Solution for injection

    Paraplatin 50mg/5mL Solution for Injection (69448-0005) (Accord BioPharma a division of Accord Healthcare, Inc.) null

    Carboplatin Solution for injection

    Paraplatin 600mg/60ml Solution for Injection (00015-3216) (Bristol Myers Squibb Oncology Products) (off market)

    Carboplatin Solution for injection

    Paraplatin 600mg/60mL Solution for Injection (69448-0005) (Accord BioPharma a division of Accord Healthcare, Inc.) null

    Carboplatin Solution for injection

    Paraplatin 50mg/5ml Solution for Injection (00015-3210) (Bristol Myers Squibb Oncology Products) (off market)

    Carboplatin Solution for injection

    Paraplatin 50mg/5ml Solution for Injection (NOVAPLUS) (00015-3210) (Bristol Myers Squibb Co) (off market)

    Carboplatin Solution for injection

    Paraplatin 150mg/15ml Solution for Injection (NOVAPLUS) (00015-3211) (Bristol Myers Squibb Co) (off market)

    Carboplatin Solution for injection

    Paraplatin 450mg/45ml Solution for Injection (NOVAPLUS) (00015-3212) (Bristol Myers Squibb Co) (off market)

    Description/Classification

    Description

    Carboplatin (CBDCA) is a platinum compound related to cisplatin. Carboplatin is formed by replacing the chloride leaving groups of cisplatin with 1, 1-cyclobutanedicarboxylato ligand, which increases the stability of the leaving groups. On a molar basis, carboplatin is 45 times less cytotoxic than cisplatin. Carboplatin has a more favorable adverse effect profile than cisplatin, which has led to the investigation of the replacement of cisplatin with carboplatin in many regimens. Carboplatin and cisplatin seem to be equally effective in ovarian, non-small cell and small cell lung cancers. Comparative trials are ongoing in these cancers and others to determine if there is an advantage of carboplatin over cisplatin. Most tumors that are resistant to cisplatin will be resistant to carboplatin. Currently, there does not seem to be a role for carboplatin in place of cisplatin in the routine management of testicular or head and neck cancers. Due to its myelosuppressive effects, carboplatin has been used in bone marrow ablation protocols and in the treatment of relapsed leukemias. The FDA approved carboplatin for the treatment of ovarian cancer in March 1989.

    Classifications

    • Antineoplastic and Immunomodulating Agents
      • Antineoplastics
        • Alkylating Agents
          • Platinum Compounds
    Revision Date: 09/11/2024, 01:56:00 AM

    References

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    Hazardous Drugs Classification

    • NIOSH 2016 List: Group 1 [63664]
    • NIOSH (Draft) 2020 List: Table 1
    • Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    • Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.[63664]

    Emetic Risk

    • Pediatrics: Doses 175 mg/m2/dose or higher: High
    • Adults: Moderate
    • Administer routine antiemetic prophylaxis prior to treatment.[67392][67389]

    Extravasation Risk

    • Irritant [67387]

    Route-Specific Administration

    Injectable Administration

    • Carboplatin is administered intravenously as an infusion.
    • Routine hydration is not required with carboplatin therapy. Hydration should be considered in patients with renal impairment or in those receiving concurrent nephrotoxic agents.
    • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    • Aluminum needles or IV sets containing aluminum should not be used for carboplatin preparation or administration because aluminum reacts with carboplatin to form a precipitate, causing loss of potency.

    Intravenous Administration

    Reconstitution of vials:

    • Reconstitute carboplatin 50 mg, 150 mg, or 450 mg vials with 5 mL, 15 mL, or 45 mL, respectively, of sterile water for injection, 5% Dextrose for injection, or 0.9% Sodium Chloride injection. The reconstituted vials should have a concentration of 10 mg/mL of carboplatin.
    • Reconstituted vials are stable for 24 hours at room temperature (25 degrees C). Paraplatin multidose (10 mg/mL) vials are stable for up to 14 days following initial entry into the vial.

     

    Further dilution for infusion:

    • Further dilute carboplatin solution (10 mg/mL) with 5% Dextrose injection or 0.9% Sodium Chloride injection to concentrations of 0.5 to 4 mg/mL.
    • Carboplatin solutions further diluted with 5% Dextrose injection or 0.9% Sodium Chloride injection are stable for 8 hours at room temperature (25 degrees C). Since carboplatin solutions are preservative-free the manufacturer recommends discarding any unused carboplatin solution after 8 hours.

     

    Intermittent infusion:

    • Infuse appropriate dose IV over 15 minutes to 1 hour.

     

    Continuous infusion:

    • Infuse at a rate to allow administration of the entire dose over a 24-hour period.

    Other Administration Route(s)

    Intraperitoneal Administration:

    NOTE: Carboplatin is not approved by the FDA for intraperitoneal administration.

    • Add carboplatin to a pre-warmed sterile 0.9% Sodium Chloride solution prior to instilling (i.e., body temperature).
    • Dilute carboplatin dosage in 2 liters 0.9% Sodium Chloride injection, instill and dwell for 2 to 4 hours, then drain by gravity as completely as possible.
    • Carboplatin is administered via a Tenckhoff catheter or a percutaneously inserted peritoneal dialysis catheter.

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Carboplatin

    pH Range
    pH 5 to 7 (1% solution)
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    Osmolality/Osmolarity
    Carboplatin reconstituted with sterile water for injection to a 10-mg/mL concentration was hypotonic having a measured osmolality of 94 mOsm/kg. Reconstituted to 15-mg/mL with sterile water for injection or sodium chloride 0.9%, the osmolalities are about 133 and 409 mOsm/kg, respectively. If diluted in dextrose 5% or sodium chloride 0.9%, the solutions would be near iso-osmotic.
    ReferencesCobb HH. Stability of fludarabine phosphate, pentostatin, and amsacrine in commonly used infusion solutions and after filtration, and osmolality of various constituted chemotherapeutic agents. Ph.D. Dissertation. 1995;
    ReferencesTrissel LA. Drug information- osmolalities. Data on file.
    Stability
    Carboplatin in intact containers stored as directed by the manufacturer is stable until the labeled expiration date. Di Pasqua et al. reported that the extended stability of carboplatin as the 10-mg/mL liquid formulation results from self-association complexes of carboplatin that do not occur to the same extent at lower concentrations. The manufacturer indicates that reconstituted carboplatin solution is stable for 8 hours at room temperature (up to 25 degree C). Because no antimicrobial preservative is present in the single-dose containers, the manufacturer recommends that the solutions be discarded after 8 hours. Other research by the National Cancer Institute demonstrated that reconstituted carboplatin in sterile water for injection underwent no decomposition in 24 hours at room temperature. Williams reported carboplatin 1 mg/mL in sterile water decomposed 10% in 14 days while carboplatin 7 mg/mL in sterile water lost only 4% in 7 days at room temperature. Northcott et al. reported similar results with no loss in 14 days refrigerated or at 37 degree C for a 1-mg/mL solution in sterile water. The introduction of the commercial carboplatin 10-mg/mL aqueous injection with an extended expiration date indicates the drug is indeed stable for extended periods in sterile water for injection. The manufacturer also states that reconstituted carboplatin 10-mg/mL aqueous injection in multiple dose vials is physically, chemically, and microbially stable for up to 14 days at 25 degree C even with multiple needle entries. Lu et al. evaluated the stability of carboplatin 5, 10, and 20 mg/mL solution in water that was heated to 60, 80, and 100 degree C for 20 minutes in a water bath. Little or no loss of carboplatin occurred when heated up to boiling for 20 minutes. Infusion Solutions: The manufacturer indicates that carboplatin may be diluted in dextrose 5% and used within 8 hours. However, several research studies have reported that carboplatin diluted in dextrose 5% is stable for much longer periods ranging from 9 days at room temperature by Benaji et al., 14 days at 37 degree C by Hadfield et al., 21 days refrigerated and at room temperature, by Diaz Amador et al., up to 28 days refrigerated, at room temperature, and at 37 degree C by Rochard et al., and up to 84 days refrigerated by Kaestner and Sewell. Prat et al. reported about 1% loss in 30 days at room temperature protected from exposure to light. Based on elevated temperature studies, Prat et al. calculated the time to 10% decomposition at room temperature to be over 300 days protected from exposure to light. The manufacturer indicates that carboplatin may be diluted in sodium chloride 0.9% and used for 8 hours. Cheung et al. and Williams both reported a somewhat more rapid loss of carboplatin in chloride-containing solutions such as sodium chloride 0.9% when compared to dextrose 5% with losses of 4 to 5% up to 8% in 24 hours at room temperature. Curis et al. reported detecting some conversion of carboplatin to cisplatin in the presence of chloride ions from excess hydrochloric acid. Gust and Schnurr reported the formation of some cisplatin (up to 2%) when carboplatin was diluted in sodium chloride 0.9%; they stated that they believe was unacceptable. However, Perrone et al. reported the amount to be much smaller indicating that very little conversion of carboplatin (less than 0.1%) to the more toxic cisplatin occurred in chloride-containing infusion solutions. Packaged in Syringes: Sewell et al. found that carboplatin 10 mg/mL packaged in plastic syringes underwent no decomposition in 5 days refrigerated and 3% loss in 24 hours at body temperature of 37 degree C. Valiere et al. reported that no physical instability or carboplatin loss was detected by HPLC analysis in 8 days at room temperature from a 10-mg/mL solution in polypropylene syringes.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesBenaji B, Dine T, Luyckx M, et al. Stability and compatibility of cisplatin and carboplatin with PVC infusion bags. J Clin Pharm Ther. 1994; 19
    ReferencesCheung YW, Cradock JC, Vishnuvajjala BR, et al. Stability of cisplatin, iproplatin, carboplatin, and tetraplatin in commonly used intravenous solutions. Am J Hosp Pharm. 1987; 124
    ReferencesCuris E, Provost K, Bouvet D, et al. Carboplatin and oxaliplatin decomposition in chloride medium, monitored by XAS. J Synchrotron Rad. 2001; 8
    ReferencesDiaz Amador F, Sevilla Azzati E, de Tejada y Lopez-Coterilla AH. Stability of carboplatin in polyvinyl chloride bags. Am J Health-Syst Pharm. 1998; 55
    ReferencesDi Pasqua AJ, Kerwood DJ, Shi Y, et al. Stability of carboplatin and oxaliplatin in their infusion solutions is due to self-association. Dalton Trans. 2011; 40
    ReferencesGust R, Schnurr B. Investigations on the stability of carboplatin infusion solutions [Untersuchungen zur stabilitat von carboplatin-infusionlosungen]. Monatshefte fur Chemie. 1999; 130
    ReferencesHadfield JA, McGown AT, Dawson MJ, et al. The suitability of carboplatin solutions for 14-day continuous infusion by ambulatory pump: an HPLC-dynamic FAB study. J Pharm Biomed Anal. 1993; 11
    ReferencesKaestner S, Sewell G. A sequential temperature cycling study for the investigation of carboplatin infusion stability to facilitate "dose banding". J Oncol Pharm Pract. 2007; 13
    ReferencesLu M, Yin X, Shen Q, et al. Intratumoral injection of boiling carboplatin (BCBP) solution for treatment of liver cancer in the animal model. Hepato-Gastroenterology. 2001; 48
    ReferencesNorthcott M, Allsopp MA, Powell H, et al. The stability of carboplatin, diamorphine, 5-fluorouracil and mitozantrone infusions in an ambulatory pump under storage and prolonged "in-use" conditions. J Clin Pharm Ther. 1991; 16
    ReferencesPerrone RK, Kaplan MA, Bogardus JB. Extent of cisplatin formation in carboplatin admixtures. Am J Hosp Pharm. 1989; 46
    ReferencesPrat J, Pujol M, Girona V, et al. Stability of carboplatin in 5% glucose solution in glass, polyethylene and polypropylene containers. J Pharm Biomed Anal. 1994; 12
    ReferencesRochard E, Barthes D, Courtois P. Stability and compatibility study of carboplatin with three portable infusion pump reservoirs. Int J Pharm. 1994; 101
    ReferencesSewell GJ, Riley CM, Rowland CG. The stability of carboplatin in ambulatory continuous infusion regimes. J Clin Pharm Ther. 1987; 12
    ReferencesTrissel LA, Flora KP, Vishnuvajjala R, et al. NCI investigational drugs pharmaceutical data. Bethesda, MD: National Cancer Institute. Data on file. 1994;
    ReferencesValiere C, Arnaud P, Caroff E, et al. Stability and compatibility study of a carboplatin solution in syringes for continuous ambulatory infusion. Int J Pharm. 1996; 138
    ReferencesWilliams DA. Stability and compatibility of admixtures of antineoplastic drugs, in Lokich JJ (ed), Cancer chemotherapy by infusion, 2nd ed. Chicago: Precept Press. 1990.
    pH Effects
    The pH range in which carboplatin exhibits maximum solution stability is pH 4 to 6.5. Above pH 6.5, carboplatin undergoes more rapid decomposition. When carboplatin was mixed with the alkaline drug fluorouracil, a pH of about 8.7 resulted. Carboplatin then decomposed rapidly and extensively at room temperature. If the solution was buffered with sterile citric acid solution to lower the solution to pH 6.5 (within the range of maximum stability), the carboplatin loss was reduced to about 3% in 48 hours.
    ReferencesAllwood M, Stanley A, Wright P. The cytotoxics handbook, 3rd ed., Oxford, England: Radcliffe Medical Press, 1997.
    ReferencesSewell GJ, Allsopp MP, Collinson MP, et al. Stability studies on admixtures of 5-fluorouracil with carboplatin and 5-fluorouracil with heparin for administration in continuous infusion regimens. J Clin Pharm Ther. 1994; 19
    ReferencesTheuer H, Scherbel G, Balzulat S, et al. Herstellung und stabilitatuntersuchungen von carboplatin iv. [Production and stability of carboplatin injection.]. Krankenhauspharmazie. 1994; 15
    Light Exposure
    The manufacturer does not indicate that protection from exposure to light is needed for normal clinical administration of carboplatin. Light protection is needed for long-term storage of intact carboplatin vials. Pujol et al. evaluated the photodegradation of aqueous carboplatin solutions exposed to light of varying light intensities from a 250W Xe lamp varying pH values of the solutions from very acidic to alkaline. Carboplatin was reported to undergo photodegradation following first-order kinetics. The rate of photodegradation was much greater at acidic pH values, especially less than pH 4. The minimum amount of photodegradation occurred at neutral pH. Torres et al. also evaluated the effect of varying light intensities from a 250W Xe lamp on the stability of carboplatin 0.8 and 3.2 mg/mL in dextrose 5% in Pyrex cells at 25 degree C. Increasing the light intensity increased the amount of decomposition and reduced the time to 10% loss of the drug. At the highest light intensity, 10% loss occurred in about 2 to 3 hours. The authors indicated that protection from exposure to light might be needed. But in a subsequent paper by Carballar et al., the researchers reevaluated the photodegradation of carboplatin 0.3 and 0.8 mg/mL in dextrose 5% using the same techniques used in the Torres et al. paper and came to a different conclusion. In this second study the research team found that photodegradation occurred, but that it was not significant at 25 degree C. How artificially induced photodegradation applies to clinical care situations in normal fluorescent room light is uncertain. But because photodegradation at some level appears to be possible, exposing carboplatin solutions to direct sunlight should be avoided and protection from exposure to light would appear to be reasonable for long-term storage of the intact vials as is stated in the manufacturer's labeling.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesCarballar R, Munoz M, Pujol M, et al. Stability study of carboplatin in aqueous solution and under illumination by high performance liquid chromatography. Biomed Chromatog. 1997; 11
    ReferencesPujol M, Part J, Trillas M, et al. Stability of aqueous carboplatin solutions under illumination. Monatschefte fur Chemie. 1993; 124
    ReferencesTorres F, Girona V, Puiol M, et al. Stability of carboplatin in 5% glucose solution exposed to light. Int J Pharm. 1996; 129
    Sorption Leaching
    Carboplatin has not been found to undergo substantial sorption to polyvinyl chloride (PVC), ethylene vinyl acetate, polyethylene, polypropylene (in syringes or bags), or glass containers, or to elastomeric pump reservoirs and to Silastic catheters.
    ReferencesAnon. Drug stability data for Intermate and Infusor portable elastomeric infusion devices. Round Lake, IL: Baxter Healthcare Corporation.. 2008;
    ReferencesBeitz C, Bertsch T, Hannak D, et al. Compatibility of plastics with cytotoxic drug solutions - comparison of polyethylene with other container materials. Int J Pharm. 1999; 185
    ReferencesBeitz C, Einberger C, Wehling M. Stabilitat und kompatibilitat von zytostatika-zubereitungen mit infusionslosungensbehaltern aus polyethylen. [Stability and compatibility of cytotoxic drug solutions with polyethylene infusion containers.]. Krankenhauspharmazie. 1999; 20
    ReferencesBenaji B, Dine T, Luyckx M, et al. Stability and compatibility of cisplatin and carboplatin with PVC infusion bags. J Clin Pharm Ther. 1994; 19
    ReferencesCheung YW, Cradock JC, Vishnuvajjala BR, et al. Stability of cisplatin, iproplatin, carboplatin, and tetraplatin in commonly used intravenous solutions. Am J Hosp Pharm. 1987; 124
    ReferencesDiaz Amador F, Sevilla Azzati E, de Tejada y Lopez-Coterilla AH. Stability of carboplatin in polyvinyl chloride bags. Am J Health-Syst Pharm. 1998; 55
    ReferencesHadfield JA, McGown AT, Dawson MJ, et al. The suitability of carboplatin solutions for 14-day continuous infusion by ambulatory pump: an HPLC-dynamic FAB study. J Pharm Biomed Anal. 1993; 11
    ReferencesKaestner S, Sewell G. A sequential temperature cycling study for the investigation of carboplatin infusion stability to facilitate "dose banding". J Oncol Pharm Pract. 2007; 13
    ReferencesNorthcott M, Allsopp MA, Powell H, et al. The stability of carboplatin, diamorphine, 5-fluorouracil and mitozantrone infusions in an ambulatory pump under storage and prolonged "in-use" conditions. J Clin Pharm Ther. 1991; 16
    ReferencesPrat J, Pujol M, Girona V, et al. Stability of carboplatin in 5% glucose solution in glass, polyethylene and polypropylene containers. J Pharm Biomed Anal. 1994; 12
    ReferencesRochard E, Barthes D, Courtois P. Stability and compatibility study of carboplatin with three portable infusion pump reservoirs. Int J Pharm. 1994; 101
    ReferencesSewell GJ, Riley CM, Rowland CG. The stability of carboplatin in ambulatory continuous infusion regimes. J Clin Pharm Ther. 1987; 12
    ReferencesValiere C, Arnaud P, Caroff E, et al. Stability and compatibility study of a carboplatin solution in syringes for continuous ambulatory infusion. Int J Pharm. 1996; 138
    Other Information
    Carboplatin is cited by NIOSH as a drug that should be handled as hazardous. Aluminum Interaction: No equipment containing aluminum should be used with carboplatin solutions. Aluminum-containing needles and other equipment may interact with carboplatin resulting in precipitation and loss of the drug. Tromethamine in Fluorouracil Formulation: Fournier et al. reported that a fluorouracil formulation containing tromethamine as a buffer of solution pH caused the loss of carboplatin due to the tromethamine content. HPLC analysis of carboplatin combined with this tromethamine-containing fluorouracil formulation demonstrated that the tromethamine caused 55% carboplatin loss in 24 hours. Quality Control: Lelievre et al. described an approach to quality control and accuracy assessment for 22 cancer chemotherapy drugs, including carboplatin, which is designed to reduce the risk of erroneously prepared doses reaching patients. The technique utilized an ultraviolet (UV)-visible and infrared (IR) scanning analysis (Multispec, Microdom) of the finished dosage forms to verify the right molecule, concentration, and solution. Of 3149 doses of the 22 drugs tested, 7.82% varied by more than 10% from the intended concentration.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesAnon. Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. NIOSH Publication No. 2004-165. 2004; 165
    ReferencesFournier C, Hecquet B, Bastian G, et al. Modification of the physicochemical and pharmacological prperties of anticancer platinum compounds by commercial 5-fluorouracil formulations: a comparative study using cisplatin and carboplatin. Cancer Chemother Pharmacol. 1992; 29
    ReferencesLelievre B, Devys C, Daouphars M, et al. Qualitative and quantitative analysis of chemotherapy preparations. Eur J Hosp Pharm Pract. 2010; 16
    Stability Max
    Maximum reported stability periods: Reconstituted in sterile water - 14 days refrigerated, at room temperature, and at 37 degree C. In D5W- 84 days, refrigerated, 30 days at room temperature, and 28 days at 37 degree C. In D5W- 10% decomposition (t90) at room temperature has been calculated to be over 300 days protected from exposure to light. In NS- 24 hours at room temperature.
    ReferencesAhmed ST, Parkinson R. The stability of drugs in pre-filled syringes: flucloxacillin, ampicillin, cefuroxime, cefotaxime, and ceftazidime. Hosp Pharm Pract. 1992; 2
    ReferencesCheung YW, Cradock JC, Vishnuvajjala BR, et al. Stability of cisplatin, iproplatin, carboplatin, and tetraplatin in commonly used intravenous solutions. Am J Hosp Pharm. 1987; 124
    ReferencesKaestner S, Sewell G. A sequential temperature cycling study for the investigation of carboplatin infusion stability to facilitate "dose banding". J Oncol Pharm Pract. 2007; 13
    ReferencesPrat J, Pujol M, Girona V, et al. Stability of carboplatin in 5% glucose solution in glass, polyethylene and polypropylene containers. J Pharm Biomed Anal. 1994; 12
    ReferencesRochard E, Barthes D, Courtois P. Stability and compatibility study of carboplatin with three portable infusion pump reservoirs. Int J Pharm. 1994; 101
    ReferencesWilliams DA. Stability and compatibility of admixtures of antineoplastic drugs, in Lokich JJ (ed), Cancer chemotherapy by infusion, 2nd ed. Chicago: Precept Press. 1990.
    Revision Date: 09/11/2024, 01:56:00 AMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

    References

    63664 - CDC National Institute for Occupational Safety and Health (NIOSH). NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2016. DHHS (NIOSH) Publication Number 2016-161, September 2016. Available on the World Wide Web at https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf?id=10.26616/NIOSHPUB201616167387 - Perez Fidalgo, JA, Garcia Fabregat L, Cervantes A, et al. Management of chemotherapy extravasation: ESMO-EONS Clinical Practice Guidelines. Ann Oncol. 2012 Oct;23 Suppl; vii167-73.67389 - Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020 Aug 20;38(24):2782-2797.67392 - Paw Cho Sing E, Robinson P, Flank J, et al. Classification of the acute emetogenicity of chemotherapy in pediatric patients: A clinical practice guideline. Pediatr Blood Cancer. 2019 May;66(5):e27646. Doi: 10.1002/pbc.27646. Epub 2019 Feb 7.

    Adverse Reactions

    Mild

    • alopecia
    • anorexia
    • asthenia
    • diarrhea
    • dysgeusia
    • infection
    • injection site reaction
    • nausea
    • pruritus
    • rash
    • urticaria
    • vomiting

    Moderate

    • anemia
    • bleeding
    • bone marrow suppression
    • constipation
    • dehydration
    • elevated hepatic enzymes
    • erythema
    • hyperbilirubinemia
    • hypertension
    • hypocalcemia
    • hypokalemia
    • hypomagnesemia
    • hyponatremia
    • hypotension
    • leukopenia
    • neutropenia
    • stomatitis
    • thrombocytopenia

    Severe

    • anemia
    • bronchospasm
    • hearing loss
    • heart failure
    • hemolytic-uremic syndrome
    • leukopenia
    • neutropenia
    • new primary malignancy
    • serious hypersensitivity reactions or anaphylaxis
    • stroke
    • thrombocytopenia
    • thromboembolism
    • tissue necrosis
    • visual impairment

    Bone marrow suppression is the dose-limiting toxicity of carboplatin and may be more severe in patients with impaired kidney function, prior therapy especially cisplatin-containing regimens, and/or who are receiving other myelosuppressive chemotherapy or radiotherapy. Myelosuppression also occurs after intraperitoneal administration of carboplatin. Thrombocytopenia (defined as < 100,000 cells/mm3; severe, < 50,000 cells/mm3), neutropenia (defined as < 2000 cells/mm3; severe, < 1000 cells/mm3), leukopenia (defined as < 4000 cells/mm3; severe, < 2000 cells/mm3), and anemia (defined as < 11 grams/dL; severe, < 8 grams/dL) have been reported. Following single-agent carboplatin, nadirs typically occur at about day 21 and most counts recover by day 28. Drug-related death has been reported in less than 1% of patients who developed infectious or hemorrhagic complications with carboplatin therapy. Neutropenic fever has been reported. Hematologic adverse effects that occurred in 1893 patients who received single-agent carboplatin for various cancer types include severe thrombocytopenia (25%), neutropenia (16%), leukopenia (15%); anemia was also reported (71%). In women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (combination arm; n = 393) or single-agent carboplatin as second-line therapy (n = 553), thrombocytopenia (combination arm, 66%; single-agent arm, 62%), neutropenia (combination arm, 96%; single-agent arm, 67%), leukopenia (combination arm, 97%; single-agent arm, 85%), and anemia (combination arm, 90%; single-agent arm, 90%) were reported. Additionally, severe thrombocytopenia (combination arm, 33%; single-agent arm, 35%), neutropenia (combination arm, 82%; single-agent arm, 21%), leukopenia (combination arm, 71%; single-agent arm, 26%), and anemia (combination arm, 14%; single-agent arm, 21%) were reported in this analysis. Monitor blood counts between courses of therapy. Treatment cycles may need to be delayed for severe myelosuppression; the carboplatin dosage may be increased or decreased based on nadir platelet and neutrophil counts.[52338]

    Gastrointestinal (GI) system adverse events that occurred in 1893 patients who received single-agent carboplatin for various cancer types include vomiting (65%), nausea (10%-15%), GI pain (17%), diarrhea (6%), and constipation (6%). Patients who had received prior chemotherapy, particularly cisplatin, or receive carboplatin in combination with other chemotherapy were more likely to experience emesis. Nausea and vomiting usually resolves within 24 hours and these symptoms often respond well to antiemetic therapy. In women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (combination arm; n = 393) or single-agent carboplatin as second-line therapy (n = 553), nausea and vomiting (combination arm, 93%; single-agent arm, 92%), vomiting (combination arm, 83%; single-agent arm, 81%), mucositis (combination arm,8 %; single-agent arm, 1%), and other GI side effects (combination arm, 46%; single-agent arm, 21%) were reported. In postmarketing surveillance, stomatitis and anorexia were reported in patients who received carboplatin.[52338]

    Electrolyte changes that occurred in 1893 patients who received single-agent carboplatin for various cancer types include abnormally decreased sodium (hyponatremia) (29%), magnesium (hypomagnesemia) (29%), calcium (hypocalcemia) (22%), and potassium (hypokalemia) (20%). These electrolyte abnormalities were usually asymptomatic. In women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (combination arm; n = 393) or single-agent carboplatin as second-line therapy (n = 553), hyponatremia (combination arm, 10%; single-agent arm, 47%), hypomagnesemia (combination arm, 61%; single-agent arm, 43%), hypocalcemia (combination arm, 16%; single-agent arm, 31%), and hypokalemia (combination arm, 16%; single-agent arm, 28%) were reported.[52338]

    Serious hypersensitivity reactions or anaphylaxis (e.g., rash (unspecified), urticaria, erythema, pruritus, and rarely bronchospasm and hypotension) were reported in 2% of patients who received single-agent carboplatin for various cancer types (n = 1893). Allergic reactions were reported in 11% of women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (n = 393) and 2% of women with ovarian cancer who received single-agent carboplatin as second-line therapy (n = 553). In postmarketing surveillance, anaphylactoid reactions were reported in patients who received carboplatin. Patients with prior exposure to platinum or platinum-containing compounds, including cisplatin, may be at increased risk for anaphylactoid reactions. Hypersensitivity usually develops after >= 6 courses of carboplatin. Manage severe reactions with epinephrine, corticosteroid, and antihistamine therapy.[52338]

    Ototoxicity and other sensory abnormalities such as visual impairment (visual disturbance) and dysgeusia (change in taste) were reported in 1% of patients who received single-agent carboplatin for various cancer types (n = 1893). Hearing loss has occurred in pediatric patients who received higher than recommended carboplatin in combination with other ototoxic drugs. Additionally, reversible or partially reversible loss of vision has occurred with higher than recommended carboplatin doses. In women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (combination arm; n = 393) or single-agent carboplatin as second-line therapy (n = 553), ototoxicity (combination arm, 12%; single-agent arm, 1%) and other sensory side effects (combination arm, 5%; single-agent arm, 1%) were reported.[52338]

    Increased alkaline phosphatase levels (24%), elevated hepatic enzymes including increased AST levels (15%), and hyperbilirubinemia (5%) were reported in patients who received single-agent carboplatin for various cancer types (n = 1893). Most hepatic adverse effects were mild and were reversible in about half the cases. Severe hepatic enzyme abnormalities have been reported with high-dose carboplatin use in patients receiving a bone marrow transplant. In women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (combination arm; n = 393) or single-agent carboplatin as second-line therapy (n = 553), increased alkaline phosphatase levels (combination arm, 29%; single-agent arm, 37%), increased AST levels (combination arm, 20%; single-agent arm, 19%), and hyperbilirubinemia (combination arm, 5%; single-agent arm, 5%) were reported.[52338]

    New primary malignancy has been reported in patients who received carboplatin-containing combination chemotherapy.[52338] In the treatment of ovarian cancer, platinum-based therapy has been associated with an increased risk of new malignancy, primarily acute myelogenous leukemia, myelodysplastic syndromes, acute lymphocytic leukemia and chronic myelogenous leukemia. The risk of new malignancy increases with cumulative carboplatin doses higher than 2,000 mg. However, in evaluating the risks versus benefits of platinum-based chemotherapy in the treatment of ovarian cancer, the survival benefits exceed the risk of new malignancy.[25494]

    Alopecia occurred in 3% of patients who received single-agent carboplatin for various cancer types (n = 1893). Additionally, alopecia was reported in 49% of women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (n = 393) and 2% of women with ovarian cancer who received single-agent carboplatin as second-line therapy (n = 553). In postmarketing surveillance, injection site reaction (e.g., redness, swelling, and pain) and tissue necrosis associated with extravasation have been reported in patients who received carboplatin.[52338]

    Increased serum creatinine (Scr) (6%) and blood urea nitrogen (BUN) (14%) levels were reported in patients who received single-agent carboplatin for various cancer types (n = 1893). Most renal adverse effects were mild and were reversible in about half the cases. A reduction in creatinine clearance (CrCl) was observed in 27% of carboplatin-treated patients who had a baseline CrCl of 60 mL/min or higher. In women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (combination arm; n = 393) or single-agent carboplatin as second-line therapy (n = 553), increased SCr (combination arm, 6%; single-agent arm, 10%) and BUN (combination arm, 17%; single-agent arm, 22%) levels were reported. Cancer-associated hemolytic-uremic syndrome occurred rarely in patients who received carboplatin. Consider lower initial doses of single-agent carboplatin in patients with a baseline CrCl less than 60 ml/min; subsequent doses may be adjusted based on individual patient tolerance (e.g., degree of myelosuppression with therapy).[52338]

    Cardiovascular toxicity was reported in 19% of women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (n = 393) and 6% of women with ovarian cancer who received single-agent carboplatin as second-line therapy (n = 553). Fatal cardiovascular events, including heart failure, thromboembolism, and cerebrovascular accidents (stroke), were reported in less than 1% of patients who received single-agent carboplatin for various cancer types (n = 1893); these events did not appear to be associated with chemotherapy use. In postmarketing surveillance, hypertension was reported in patients who received carboplatin.[52338]

    In postmarketing surveillance, dehydration was reported in patients who received carboplatin.[52338]

    Infectious or hemorrhagic complications with carboplatin therapy occurred in 5% of patients who received single-agent carboplatin for various cancer types (n = 1893); drug-related death has been reported in less than 1% of these patients. In women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (combination arm; n = 393) or single-agent carboplatin as second-line therapy (n = 553), bleeding (combination arm, 8%; single-agent arm, 5%) and transfusions (combination arm, 35%; single-agent arm, 44%) were reported. In this study, infection was reported in 16% of women who received carboplatin plus cyclophosphamide and 5% of women who received single-agent carboplatin as second-line therapy.[52338]

    Asthenia was reported in 41% of women with ovarian cancer who received carboplatin plus cyclophosphamide as first-line therapy in 2 randomized studies (n = 393) and 11% of women with ovarian cancer who received single-agent carboplatin as second-line therapy (n = 553).[52338]

    Revision Date: 09/11/2024, 01:56:00 AM

    References

    25494 - Travis LB, Holowaty EJ, Bergfeldt K, et al. Risk of leukemia after platinum-based chemotherapy for ovarian cancer. N Engl J Med 1999;340:351-7.52338 - Carboplatin injection package insert. Princeton, NJ: Sandoz Inc;2011 Dec.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • bleeding
    • bone marrow suppression
    • platinum compound hypersensitivity
    • anemia
    • anuria
    • breast-feeding
    • children
    • coagulopathy
    • dialysis
    • geriatric
    • hearing impairment
    • herpes infection
    • infection
    • neutropenia
    • peripheral neuropathy
    • pregnancy
    • radiation therapy
    • renal failure
    • renal impairment
    • requires a specialized care setting
    • requires an experienced clinician
    • serious hypersensitivity reactions or anaphylaxis
    • thrombocytopenia
    • varicella
    • viral infection
    • vomiting

    Carboplatin is contraindicated in patients who exhibit platinum compound hypersensitivity. For example, patients who have worked with platinum in the electronics industry can develop sensitivity to platinum. There is an increased incidence of hypersensitivity reactions in patients previously exposed to platinum therapy. Serious hypersensitivity reactions or anaphylaxis may occur within minutes of carboplatin administration. Epinephrine, corticosteroids, and antihistamines have been utilized to treat these reactions.

    Contraindications to carboplatin include patients with severe bone marrow suppression and significant bleeding; patients with acute leukemia may require treatment with carboplatin despite severe bone marrow suppression. Carboplatin-induced bone marrow suppression is dose-related and is dose limiting. Complete blood counts should be frequently monitored during carboplatin treatment and, when appropriate, until recovery is achieved. Single intermittent courses of carboplatin should not be repeated until leukocyte, neutrophil, and platelet counts have recovered. When used in combination with other myelosuppressive chemotherapy agents, the dose and administration of carboplatin must be carefully reviewed and adjusted to minimize additive effects. Carboplatin should be used cautiously in patients with coagulopathy, reduced renal function, or in those who have received previous cisplatin or myelosuppressive therapy such as chemotherapy or radiation therapy; these patients may require reduced dosages (i.e., lower target AUC values). Carboplatin is a radiation sensitizer and patients may experience severe myelosuppression or other toxicities with concurrent use. Patients with preexisting bone marrow suppression should be allowed to recover their counts prior to carboplatin administration. Severe thrombocytopenia (< 50,000/mm3) or neutropenia (< 500/mm3) following carboplatin treatment indicates the need for a dose reduction for subsequent courses. Anemia is cumulative; transfusions or use of red blood cell growth factors may be needed during carboplatin therapy, especially during prolonged treatment. Patients with an active infection should be treated prior to receiving carboplatin when possible. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.

    Due to extensive renal elimination, carboplatin dosage should be adjusted in patients with renal impairment or renal failure, including anuria, to avoid excessive myelosuppressive effects. Patients on dialysis have received carboplatin but at reduced doses. Previous therapy with nephrotoxic agents such as cisplatin or aminoglycosides may increase the incidence of nephrotoxicity. Hydration prior to treatment may lessen the nephrotoxic effects in patients with renal impairment or in those who are receiving nephrotoxic agents concurrently. Hydration should be given with high-dose carboplatin to decrease nephrotoxicity.

    Carboplatin should be used with caution in patients with hearing impairment. Children are at increased risk of clinically apparent hearing loss, especially when receiving high-dose carboplatin. Concomitant use of other ototoxic agents (e.g., aminoglycosides) should be avoided.

    Patients over the age of 65 years and patients previously treated with cisplatin tend to be at increased risk of developing peripheral neuropathy during carboplatin therapy. Preexisting peripheral neuropathy due to cisplatin does not worsen in about 70% of patients receiving carboplatin.[46283]

    Carboplatin is classified as FDA pregnancy risk category D. Carboplatin is embryotoxic and teratogenic in animal models. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Females of childbearing potential should be advised to avoid becoming pregnant during treatment with carboplatin.[46283]

    It is not known if carboplatin is excreted in breast milk. Women should stop breast-feeding while receiving carboplatin due to the potential harm to the infant.[46283]

    Carboplatin therapy requires an experienced clinician in the management of cancer chemotherapy. Carboplatin administration requires a specialized care setting adequate for the appropriate management of carboplatin therapy and complications.[29203]

    Geriatric patients treated with cisplatin tend to be at increased risk of developing peripheral neuropathy during carboplatin therapy. Preexisting peripheral neuropathy due to cisplatin does not worsen in about 70% of patients receiving carboplatin. Poor performance status may increase the risk of other toxicities, such as bone marrow suppression.[46283]

    Vomiting occurs frequently with carboplatin therapy; ensure that patients are premedicated with appropriate antiemetic therapy prior to initiating therapy with carboplatin.[60747]

    Revision Date: 09/11/2024, 01:56:00 AM

    References

    29203 - Paraplatin (carboplatin) package insert. Princeton, NJ: Bristol-Meyers Squibb Oncology; 2004 January.46283 - Carboplatin package insert. Bedford, OH: Bedford Laboratories;2009 Oct.60747 - Carboplatin injection package insert. Irvine, CA: Teva Parenteral Medicines, Inc; 2011 Oct.

    Mechanism of Action

    Carboplatin cytotoxic activity is similar to cisplatin as it binds with DNA to form intrastrand crosslinks and adducts that cause changes in the conformation of the DNA and affect DNA replication. Carboplatin readily crosses the cell membrane. Once inside the cell, the ring structure of carboplatin is hydroxylated by water to form the active moiety. This reaction occurs more slowly than the activation of cisplatin. Therefore, 4—6 times the amount of carboplatin is required to produce the same cytotoxic effects as cisplatin. Once in the active form, carboplatin functions similarly to cisplatin and binds with DNA, RNA, or other macromolecules at two sites to form interstrand and intrastrand links. Carboplatin forms irreversible covalent bonds which inhibit DNA replication, RNA transcription, and protein synthesis. Intrastrand crosslinks at the N7 position of guanine are the predominant binding sites. The maximal DNA crosslinks occur 18 hours after exposure to carboplatin compared to 6—12 hours for cisplatin. Carboplatin crosslinks have a slower removal rate than do cisplatin-induced crosslinks. This slower rate of onset and removal of carboplatin crosslinks is thought to be due to a slow rate of monofunctional adduct formation and/or a slower rate of conversion of monoadducts to crosslinks.[25915] While considered cell cycle non-specific, carboplatin cytotoxicity is increased with exposure during the S-phase and with increased infusion rates (24 hours versus 1 hour). Carboplatin causes cell cycle arrest in the G2-phase and then induces programmed cell death or apoptosis.

    Revision Date: 09/11/2024, 01:56:00 AM

    References

    25915 - Micetick KC, Barnes D, Erickson LC. A comparative study of the cytotoxicity and DNA-damaging effects of cis-(dimamino)(1,1-cyclobutanedicarboxylato)-platinum (II) and cis-diamminedichloroplatinum (II) on L1210 cells. Cancer Res 1985;45:4043-4047.

    Pharmacokinetics

    Carboplatin is primarily administered by IV infusion. The pharmacokinetics of carboplatin and cisplatin differ greatly. Very little protein binding occurs. Carboplatin distributes well into ascites and pleural fluid. CSF concentrations are approximately 30% of plasma concentrations. Carboplatin is not metabolized but undergoes spontaneous hydrolysis to form the active compound. The excretion of carboplatin is biphasic with half-lives of 90 and 180 minutes Carboplatin is excreted primarily by the kidneys via tubular filtration and secretion. Sixty-five percent of a dose can be recovered in the urine in the first 24 hours.

     

    The exposure to carboplatin or AUC is associated with myelosuppressive and cytotoxic effects. In general, carboplatin AUC of 4—7 is associated with acceptable myelosuppressive effects and efficacy. A carboplatin AUC of > 7 is associated with an increased incidence of severe myelosuppression with no added efficacy. Carboplatin bolus doses of 400—600 mg/m2 are associated with an AUC of 6—8 mg/mL x min in previously untreated patients with normal creatinine clearance. Several equations have been developed to individualize carboplatin dosing. The Calvert equation is the simplest equation and was approved by the FDA in 1995 for dosing of carboplatin. In the determination of this equation, creatinine clearance was determined using [23509]Cr-EDTA, which is thought to more accurately reflect glomerular filtration rate in patients with altered renal function than does a measured or a calculated creatinine clearance.[25916] Currently, [23509]Cr-EDTA is not available in the United States and creatinine clearance is determined using measured or calculated methods, which may not be as accurate. The Egorin equations use creatinine clearance and a relationship with platelet nadir to determine the carboplatin dosage. These equations also differentiate between previously treated and untreated patients to take into account the cumulative bone marrow toxicity of carboplatin.[25917] The dosing of carboplatin in many disease states is now almost entirely based upon AUC and not body surface area.

    Route-Specific Pharmacokinetics

    Intravenous Route

    An IV dose of carboplatin distributes widely throughout the body tissues, and distribution is equal to the total body water.

    Special Populations

    Renal Impairment

    Dosages should be reduced in patients with renal dysfunction. Hemodialysis removes carboplatin at a rate 25% that of the kidney. Dosages should be adjusted based upon the length of dialysis. Peritoneal dialysis does not remove carboplatin.

    Pediatrics

    The pharmacokinetics of carboplatin in children and adults are similar.

    Revision Date: 09/11/2024, 01:56:00 AM

    References

    23509 - DeVito JM, Vance JR. Furosemide-associated ototoxicity. Clin Pharm 1983;2:507-9.25916 - Calvert AH, Newell DR, Frumbrell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 1989;7:1748-1756.25917 - Egorin MJ, VanEcho DA, Olman EA, et al. Prospective validation of a pharmacologically based dose scheme for the cis-diamminedichloroplatinum (II) analogue diamminecyclobutanedicarboxylatoplatinum. Cancer Res 1985;45:6502-6506.

    Pregnancy/Breast-feeding

    pregnancy

    Carboplatin is classified as FDA pregnancy risk category D. Carboplatin is embryotoxic and teratogenic in animal models. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Females of childbearing potential should be advised to avoid becoming pregnant during treatment with carboplatin.[46283]

    breast-feeding

    It is not known if carboplatin is excreted in breast milk. Women should stop breast-feeding while receiving carboplatin due to the potential harm to the infant.[46283]

    Revision Date: 09/11/2024, 01:56:00 AM

    References

    46283 - Carboplatin package insert. Bedford, OH: Bedford Laboratories;2009 Oct.

    Interactions

    Level 1 (Severe)

    • Dengue Tetravalent Vaccine, Live
    • Mycophenolate

    Level 2 (Major)

    • Aldesleukin, IL-2
    • Capreomycin
    • Clozapine
    • Colistimethate, Colistin, Polymyxin E
    • Colistin
    • Ethotoin
    • Fosphenytoin
    • Hydantoins
    • Phenytoin
    • Polymyxin B

    Level 3 (Moderate)

    • Amikacin
    • Aminoglycosides
    • Bictegravir; Emtricitabine; Tenofovir Alafenamide
    • Cholera Vaccine
    • Clindamycin
    • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
    • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
    • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Emtricitabine; Rilpivirine; Tenofovir alafenamide
    • Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate
    • Emtricitabine; Tenofovir alafenamide
    • Emtricitabine; Tenofovir Disoproxil Fumarate
    • Gentamicin
    • Lamivudine; Tenofovir Disoproxil Fumarate
    • Paromomycin
    • Plazomicin
    • SARS-CoV-2 (COVID-19) vaccines
    • SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine
    • SARS-CoV-2 Virus (COVID-19) mRNA Vaccine
    • SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine
    • Streptomycin
    • Tacrolimus
    • Tenofovir Alafenamide
    • Tenofovir Alafenamide
    • Tenofovir Disoproxil Fumarate
    • Tobramycin
    • Tuberculin Purified Protein Derivative, PPD
    • Voclosporin

    Level 4 (Minor)

    • Paclitaxel
    Aldesleukin, IL-2: (Major) Avoid concomitant use of carboplatin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. [41853] [60747] Amikacin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely. [46283] Aminoglycosides: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely. [46283] Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [46283] [60269] [60688] Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including carboplatin, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. [44155] [5941] Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine. [60871] Clindamycin: (Moderate) Concomitant use of carboplatin and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. [29120] [60747] cloZAPine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist. [28262] Colistimethate, Colistin, Polymyxin E: (Major) Both colistimethate sodium and carboplatin can cause nephrotoxicity. The coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. [46283] [47035] Colistin: (Major) Both colistimethate sodium and carboplatin can cause nephrotoxicity. The coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. [46283] [47035] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [46283] [60269] [60688] Dengue Tetravalent Vaccine, Live: (Contraindicated) Avoid administration of the live dengue virus vaccine with immunosuppressive drug therapy and prior to immune recovery following treatment with immunosuppressive drug therapy. When feasible, administer indicated live virus vaccines at least 4 weeks before planned immunosuppression or wait until at least 3 months after discontinuation. The time to restoration of immune competence may be longer in some patients. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence. [60092] [64100] [65107] Doravirine; lamiVUDine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus. [46283] [51664] Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus. [46283] [51664] Efavirenz; lamiVUDine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus. [46283] [51664] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [46283] [60269] [60688] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus. [46283] [51664] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [46283] [60269] [60688] Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus. [46283] [51664] Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [46283] [60269] [60688] Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus. [46283] [51664] Ethotoin: (Major) Patients receiving antineoplastic agents concurrently with hydantoins may be at risk for toxicity or loss of clinical efficacy and seizures; anticonvulsant therapy should be monitored closely during and after administration of antineoplastic agents. Concurrent therapy with phenytoin and carboplatin has been associated with subtherapeutic phenytoin serum concentrations and seizure activity. Phenytoin dosage increases of 20 to 100% have been required in some patients, depending on the chemotherapy administered. [5110] [5510] Fosphenytoin: (Major) Patients receiving antineoplastic agents concurrently with hydantoins may be at risk for toxicity or loss of clinical efficacy and seizures; anticonvulsant therapy should be monitored closely during and after administration of antineoplastic agents. Concurrent therapy with phenytoin and carboplatin has been associated with subtherapeutic phenytoin serum concentrations and seizure activity. Phenytoin dosage increases of 20 to 100% have been required in some patients, depending on the chemotherapy administered. [5110] [5510] Gentamicin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely. [46283] Hydantoins: (Major) Patients receiving antineoplastic agents concurrently with hydantoins may be at risk for toxicity or loss of clinical efficacy and seizures; anticonvulsant therapy should be monitored closely during and after administration of antineoplastic agents. Concurrent therapy with phenytoin and carboplatin has been associated with subtherapeutic phenytoin serum concentrations and seizure activity. Phenytoin dosage increases of 20 to 100% have been required in some patients, depending on the chemotherapy administered. [5110] [5510] lamiVUDine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus. [46283] [51664] Mycophenolate: (Contraindicated) Concurrent use of carboplatin with other agents that cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects. [5941] PACLitaxel: (Minor) In vitro studies have shown an increase in cytotoxicity with either the simultaneous or sequential administration of paclitaxel and carboplatin. It appears that paclitaxel followed by carboplatin is more cytotoxic. The pharmacokinetics of either agent is not affected by this sequence of administration. [2563] [5949] Paromomycin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely. [46283] Phenytoin: (Major) Patients receiving antineoplastic agents concurrently with hydantoins may be at risk for toxicity or loss of clinical efficacy and seizures; anticonvulsant therapy should be monitored closely during and after administration of antineoplastic agents. Concurrent therapy with phenytoin and carboplatin has been associated with subtherapeutic phenytoin serum concentrations and seizure activity. Phenytoin dosage increases of 20 to 100% have been required in some patients, depending on the chemotherapy administered. [5110] [5510] Plazomicin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely. [46283] Polymyxin B: (Major) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic polymyxins like Polymyxin B injection, can have a greater risk of developing carboplatin-induced nephrooxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely. [46283] SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] Streptomycin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely. [46283] Tacrolimus: (Moderate) Concurrent use of carboplatin with other agents that cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects. [5941] Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [46283] [60269] [60688] Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. [46283] [60269] [60688] Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as carboplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus. [46283] [51664] Tobramycin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely. [46283] Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy. [43298] [43299] Voclosporin: (Moderate) Concomitant use of voclosporin and carboplatin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. [60747] [66336]
    Revision Date: 09/11/2024, 01:56:00 AM

    References

    2563 - Giaccone G, Huizing M, Postmus PE, et al. Dose-finding and sequencing study of paclitaxel and carboplatin in non-small cell lung cancer. Semin Oncol 1995;22(Suppl 9):78-82.5110 - Phillips E, Rachlis A, Ito S. Digoxin toxicity and ritonavir: a drug interaction mediated through p-glycoprotein? AIDS 2003;17:1577-8.5510 - Sylvester RK, Lewis FB, Caldwell KC, et al. Impaired phenytoin bioavailability secondary to cisplatinum, vinblastine, and bleomycin. Ther Drug Monit. 1984;6:302-5.5941 - Paraplatin (carboplatin) package insert. Princeton, NJ: Bristol-Meyers Squibb Oncology; 2004 January.5949 - Baker AF, Dorr RT. Drug interactions with the taxanes: clinical implications. Cancer Treat Rev 2001;27:221-33.28262 - Clozaril (clozapine) tablets package insert. Rosemont, PA: HLS Therapeutics (USA), Inc.; 2024 Sept.29120 - Cleocin (clindamycin injection) package insert. New York, NY: Pharmacia and Upjohn Company; 2022 May.41853 - Proleukin (aldesleukin) package insert. Malvern, PA: Clinigen, Inc.; 2023 Sept.43298 - Aplisol (tuberculin purified protein derivative, diluted) package insert. Chestnut Ridge, NY: Par Pharmaceuticals; 2016 Mar.43299 - Tubersol (tuberculin purified protein derivative, mantoux) package insert. Swiftwater, PA: Sanofi Pasteur, Inc.; 2020 Nov.44155 - Capastat (capreomycin sulfate injection) package insert. Lake Forest, IL: Akorn, Inc.; 2023 Jan.46283 - Carboplatin package insert. Bedford, OH: Bedford Laboratories;2009 Oct.47035 - Coly-Mycin M (colistimethate inj) package insert. Chestnut Ridge, NY: Par Pharmaceuticals Companies, Inc.; 2017 Apr.51664 - Stribild (elvitegravir; cobicistat; emtricitabine; tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.60092 - Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014; 58: e44-100.60269 - Genvoya (elvitegravir; cobicistat; emtricitabine; tenofovir alafenamide) package insert. Foster City, CA: Gilead Sciences, Inc; 2022 Jan.60688 - Descovy (emtricitabine; tenofovir alafenamide) package insert. Foster City, CA: Gilead Sciences, Inc.; 2022 Jan.60747 - Carboplatin injection package insert. Irvine, CA: Teva Parenteral Medicines, Inc; 2011 Oct.60871 - Vaxchora (Cholera Vaccine, live, oral) package insert. Redwood City, CA: Emergent Travel Health Inc.; 2024 Jan.64100 - Dengvaxia (dengue tetravalent vaccine, live) package insert. Swiftwater, PA: Sanofi Pasteur Inc.; 2023 August.65107 - Kroger A, Bahta L, Hunter P. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). Accessed April 25, 2024. Available at https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html.66080 - Food and Drug Administration (FDA). Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization (EUA) of Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Disease 2019 (COVID-19) for 12 years and older. Purple cap and purple border. Retrieved November 22, 2022.66336 - Lupkynis (voclosporin) capsules package insert. Rockville, MD: Aurinia Pharma U.S., Inc.; 2024 Apr.

    Monitoring Parameters

    • CBC with differential
    • serum calcium
    • serum creatinine/BUN
    • serum magnesium
    • serum phosphate
    • serum potassium
    • serum sodium
    • serum uric acid

    US Drug Names

    • Paraplatin
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