English
Treatment options depend on histologic subtype (squamous cell carcinoma or adenocarcinoma), stage at diagnosis, and medical fitness of patient r1
Consider preoperative nutritional support via nasoduodenal or jejunostomy tube; percutaneous endoscopic gastrostomy is not recommended r2
Patients may be classified into 2 groups after initial workup: r2
Locoregional cancer
Unresectable or metastatic disease r2
Drug therapy
Medication | Common regimens | Life-threatening or dose-limiting adverse reactions | Notable or nonemergent adverse reactions | Special considerations |
---|---|---|---|---|
Alkylating agent - platinum | ||||
Carboplatin | • Carboplatin + paclitaxel | • Anaphylaxis • Bone marrow suppression • Nausea/vomiting • Nephrotoxicity | • Electrolyte loss • Ototoxicity • Peripheral neuropathy • Secondary malignancy | • Avoid coadministering nephrotoxic or ototoxic agents • Ensure adequate hydration |
Cisplatin | • Capecitabine + cisplatin +/- trastuzumab +/- pembrolizumab • Cisplatin + irinotecan • Fluorouracil + cisplatin +/- trastuzumab +/- pembrolizumab | • Anaphylaxis • Bone marrow suppression • Nausea/vomiting • Nephrotoxicity • Ocular toxicity | • Electrolyte loss • Ototoxicity • Peripheral neuropathy • Secondary malignancy | • Avoid coadministering nephrotoxic or ototoxic agents • Ensure adequate hydration • Cisplatin has been associated with optic neuritis, papilledema, vision loss • Effective contraception required during and after therapy for 14 months for females of reproductive potential and for 11 months for males with female partners of reproductive potential |
Oxaliplatin | • Capecitabine + oxaliplatin + nivolumab • Capecitabine + oxaliplatin + trastuzumab +/- pembrolizumab • Fluorouracil + oxaliplatin + nivolumab • Fluorouracil + oxaliplatin +/- trastuzumab +/- pembrolizumab • FLOT (fluorouracil + oxaliplatin + docetaxel) | • Anaphylaxis • Bleeding • Bone marrow suppression • Nausea/vomiting • Posterior reversible encephalopathy syndrome (PRES) • Pulmonary fibrosis • QT prolongation and ventricular arrhythmias • Rhabdomyolysis | • Diarrhea • Fatigue • Increased hepatic enzymes • Peripheral sensory neuropathy • Stomatitis | • Effective contraception required during and after therapy for 9 months for females of reproductive potential and for 6 months for males with female partners of reproductive potential |
Antimetabolite - nucleoside metabolic inhibitor | ||||
Capecitabine | • Capecitabine + oxaliplatin +/- trastuzumab +/- pembrolizumab • Capecitabine + cisplatin +/- trastuzumab +/- pembrolizumab • Capecitabine + oxaliplatin + nivolumab | • Bone marrow suppression • Cardiotoxicity • Dehydration • Dermatologic toxicity • Hyperbilirubinemia • Renal failure | • Abdominal pain • Diarrhea • Fatigue/weakness • Nausea • Vomiting | • Increased risk of serious or fatal adverse reactions in patients with low or absent dihydropyrimidine dehydrogenase activity • Effective contraception required during and after therapy for 6 months for females of reproductive potential and for 3 months for males with female partners of reproductive potential |
Fluorouracil | • Fluorouracil + irinotecan • Fluorouracil + oxaliplatin +/- trastuzumab +/- pembrolizumab • Fluorouracil + cisplatin +/- trastuzumab +/- pembrolizumab • Fluorouracil + oxaliplatin + nivolumab • FLOT (fluorouracil + oxaliplatin + docetaxel) | • Bone marrow suppression • Cardiotoxicity • Diarrhea • Hyperammonemic encephalopathy • Mucositis • Neurotoxicity • Palmar-plantar erythrodysesthesia (hand-foot syndrome) | • Increased risk of serious or fatal adverse reactions in patients with low or absent dihydropyrimidine dehydrogenase activity • Effective contraception required during and after therapy for 3 months for females of reproductive potential and males with female partners of reproductive potential | |
HER2/neu receptor antagonist | ||||
Trastuzumab | • Capecitabine + cisplatin +/- trastuzumab +/- pembrolizumab • Capecitabine + oxaliplatin +/- trastuzumab +/- pembrolizumab • Fluorouracil + cisplatin +/- trastuzumab +/- pembrolizumab • Fluorouracil + oxaliplatin +/- trastuzumab +/- pembrolizumab | • Cardiomyopathy • Infusion-related reactions • Neutropenia • Pulmonary toxicity | • Anemia • Chills • Cough • Diarrhea • Dysgeusia • Fatigue • Fever • Headache • Infection • Insomnia • Mucosal inflammation • Nasopharyngitis • Nausea • Rash • Stomatitis • Thrombocytopenia • Weight loss | • Effective contraception required during and after therapy for 7 months for females of reproductive potential |
HER2-directed antibody and topoisomerase inhibitor conjugate | ||||
Fam-trastuzumab deruxtecan | • Fam-trastuzumab deruxtecan monotherapy | • Bone marrow suppression • Cardiomyopathy • Interstitial lung disease (ILD)/pneumonitis | • Alopecia • Anorexia • Constipation • Diarrhea • Fatigue • Fever • Hyperbilirubinemia • Hypokalemia • Increased hepatic enzymes • Musculoskeletal pain • Nausea/vomiting • Respiratory infection | • Effective contraception required during and after therapy for 7 months for females of reproductive potential and for 4 months for males with female partners of reproductive potential |
Human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody | ||||
Ipilimumab | • Nivolumab + ipilimumab | • Adrenal insufficiency • Colitis • Diabetic ketoacidosis • Exfoliative dermatitis • Hepatitis • Hyperthyroidism • Hypophysitis • Hypothyroidism • Infusion-related reactions • Myocarditis • Nephritis • Neurotoxicity • Ocular toxicity • Pneumonitis • Thyroiditis | • Anorexia • Diarrhea • Fatigue • Fever • Headache • Insomnia • Nausea/vomiting • Pruritus • Rash • Weight loss | • Effective contraception required during and after therapy for 3 months for females of reproductive potential |
Kinase inhibitor | ||||
Dabrafenib | • Dabrafenib + trametinib | • Bleeding • Cardiomyopathy • Dermatologic toxicity • Fever • New primary malignancy • Uveitis | • Alopecia • Arthralgia • Headache • Hyperglycemia • Hyperkeratosis • Papilloma | • Potential risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency • Effective non-hormonal contraception required during and after therapy for at least 2 weeks for females of reproductive potential and males with female partners of reproductive potential |
Entrectinib | • Entrectinib monotherapy | • Bone marrow suppression • Heart failure • Hepatotoxicity • Hyperuricemia • Neurotoxicity • QT prolongation • Skeletal fractures • Vision disorders | • Arthralgia • Cognitive impairment • Constipation • Cough • Diarrhea • Dizziness • Dysesthesia • Dysgeusia • Dyspnea • Edema • Fatigue • Fever • Increased hepatic enzymes • Myalgia • Nausea/vomiting • Weight gain | • Drug interactions: may need to avoid or adjust dosage of certain drugs • Effective contraception required during and after therapy for at least 5 weeks for females of reproductive potential and for 3 months for males with female partners of reproductive potential |
Larotrectinib | • Larotrectinib monotherapy | • Hepatotoxicity • Neurotoxicity | • Constipation • Cough • Diarrhea • Dizziness • Fatigue • Increased hepatic enzymes • Nausea/vomiting | • Drug interactions: may need to avoid or adjust dosage of certain drugs • Effective contraception required during and after therapy for at least 1 week for females of reproductive potential and males with female partners of reproductive potential |
Selpercatinib | • Selpercatinib monotherapy | • Bleeding • Hepatotoxicity • Hypersensitivity reactions • Hypertension • Hypothyroidism • Impaired wound healing • Interstitial lung disease (ILD)/pneumonitis • QT prolongation • Tumor lysis syndrome | • Abdominal pain • Constipation • Diarrhea • Dry mouth • Edema • Fatigue • Headache • Hypertension • Hypocalcemia • Hyponatremia • Increased hepatic enzymes • Lymphopenia • Nausea • Rash | • Drug interactions: may need to avoid or adjust dosage of certain drugs • Withhold therapy for at least 1 week prior to elective surgery and at least 2 weeks after major surgery and until adequate wound healing • Effective contraception required during and after therapy for 1 week for females of reproductive potential and males with female partners of reproductive potential |
Trametinib | • Dabrafenib + trametinib | • Bleeding • Cardiomyopathy • Colitis and gastrointestinal perforation • Dermatologic toxicity • Fever • Interstitial lung disease (ILD)/pneumonitis • New primary malignancy • Retinal pigment epithelial detachment (RPED) • Retinal vein occlusion (RVO) • Venous thromboembolism (VTE) | • Diarrhea • Hyperglycemia • Lymphedema • Rash | • Effective contraception required during and after therapy for 4 months for females of reproductive potential and males with female partners of reproductive potential |
Microtubule inhibitor | ||||
Docetaxel | • Docetaxel monotherapy • FLOT (fluorouracil + oxaliplatin + docetaxel) | • Asthenia • Bone marrow suppression • Cystoid macular edema • Dermatologic toxicity • Diarrhea • Edema • Enterocolitis and neutropenic colitis • Febrile neutropenia • Hepatotoxicity • Hypersensitivity reactions • Infections • Neurotoxicity • Stomatitis/mucositis • Toxic deaths | • Alopecia • Anorexia • Constipation • Dysgeusia • Dyspnea • Myalgia • Nail disorders • Nausea/vomiting • Pain • Secondary malignancy | • Drug interactions: may need to avoid or adjust dosage of certain drugs • Some docetaxel injection formulations contain alcohol and may impact the central nervous system and ability to drive or operate machinery • Effective contraception required during and after therapy for 6 months for females of reproductive potential and for 3 months for males with female partners of reproductive potential |
Paclitaxel | • Carboplatin + paclitaxel • Ramucirumab + paclitaxel | • Anaphylaxis • Bone marrow suppression • Cardiotoxicity • Neurotoxicity | • Alopecia • Arthralgia • Diarrhea • Increased hepatic enzymes • Injection site reactions • Mucositis • Myalgia • Nausea/vomiting | • Some paclitaxel formulations contain alcohol and may impact the central nervous system and ability to drive or operate machinery |
Nucleoside metabolic inhibitor and thymidine phosphorylase inhibitor | ||||
Trifluridine and tipiracil | • Trifluridine and tipiracil monotherapy | • Bone marrow suppression • Diarrhea • Febrile neutropenia • Nausea/vomiting | • Anorexia • Asthenia/fatigue • Fever | • Effective contraception required during and after therapy for at least 6 months for females of reproductive potential and for at least 3 months for males with female partners of reproductive potential |
Programmed death receptor-1 (PD-1) blocking antibody | ||||
Dostarlimab | • Dostarlimab monotherapy | • Adrenal insufficiency • Colitis • Diabetic ketoacidosis • Exfoliative dermatitis • Hepatitis • Hyperthyroidism • Hypophysitis • Hypothyroidism • Infusion-related reactions • Myocarditis • Nephritis • Pneumonitis • Thyroiditis | • Anemia • Asthenia • Diarrhea • Fatigue • Nausea | • Effective contraception required during and after therapy for 4 months for females of reproductive potential |
Nivolumab | • Capecitabine + oxaliplatin + nivolumab • Fluorouracil + oxaliplatin + nivolumab • Nivolumab + ipilimumab | • Adrenal insufficiency • Colitis • Diabetic ketoacidosis • Exfoliative dermatitis • Hepatitis • Hyperthyroidism • Hypophysitis • Hypothyroidism • Infusion-related reactions • Myocarditis • Nephritis • Neurotoxicity • Pneumonitis • Thyroiditis | • Abdominal pain • Anorexia • Arthralgia • Asthenia • Back pain • Constipation • Cough • Diarrhea • Dyspnea • Fatigue • Fever • Headache • Myalgia • Nausea/vomiting • Pruritus • Rash • Upper respiratory tract infection • Urinary tract infection | • Effective contraception required during and after therapy for at least 5 months for females of reproductive potential |
Pembrolizumab | • Capecitabine + cisplatin +/- trastuzumab +/- pembrolizumab • Capecitabine + oxaliplatin +/- trastuzumab +/- pembrolizumab • Fluorouracil + cisplatin +/- trastuzumab +/- pembrolizumab • Fluorouracil + oxaliplatin +/- trastuzumab +/- pembrolizumab | • Adrenal insufficiency • Anaphylaxis • Colitis • Diabetic ketoacidosis • Exfoliative dermatitis • Hepatitis • Hyperthyroidism • Hypophysitis • Hypothyroidism • Myocarditis • Nephritis • Pneumonitis • Thyroiditis | • Abdominal pain • Anorexia • Constipation • Cough • Diarrhea • Dyspnea • Fatigue • Fever • Myalgia • Nausea • Pruritus • Rash | • Effective contraception required during and after therapy for at least 4 months for females of reproductive potential |
Topoisomerase I inhibitor | ||||
Irinotecan | • Cisplatin + irinotecan • Fluorouracil + irinotecan • Irinotecan monotherapy | • Anaphylaxis • Bone marrow suppression • Diarrhea • Interstitial pulmonary disease • Renal failure | • Abdominal pain • Alopecia • Anorexia • Asthenia • Constipation • Fever • Nausea/vomiting • Weight loss | • Increased risk of neutropenia in patients with reduced UGT1A1 activity • Effective contraception required during and after therapy for at least 6 months for females of reproductive potential and for 3 months for males with female partners of reproductive potential |
Vascular endothelial growth factor receptor 2 (VEGFR2) antagonist | ||||
Ramucirumab | • Ramucirumab + paclitaxel | • Arterial thromboembolic events • Bleeding • Gastrointestinal perforation • Hepatotoxicity • Hypertension • Hypothyroidism • Impaired wound healing • Infusion-related reactions • Nephrotoxicity and proteinuria • Posterior reversible encephalopathy syndrome (PRES) | • Abdominal pain • Anorexia • Ascites • Diarrhea • Fatigue • Hypoalbuminemia • Hyponatremia • Peripheral edema • Nausea • Thrombocytopenia | • Withhold therapy for at least 28 days prior to elective surgery and for at least 2 weeks after major surgery and until adequate wound healing • Effective contraception required during and after therapy for 3 months for females of reproductive potential |
Advise smoking cessation and counseling, if indicated r2
Palliative interventions r2r38
Supportive care