Trimodality therapy with cisplatin plus fluorouracil chemotherapy with concurrent radiotherapy followed by surgery for esophageal and esophagogastric junction cancer^[1]

Dilute each day's dose in 500 to 1000 mL D5W* and administer as a continuous infusion over 24 hours per day for four days (96 hours). Begin each course after completion of cisplatin.

• IV fluid to establish a urine flow of at least 100 mL/hour for at least two hours prior to and two hours after cisplatin administration.
• Alternative: Pretreatment hydration with 1 to 2 L of IV fluid infused for 8 to 12 hours prior to each dose of cisplatin.^[2]
• Refer to UpToDate topics on cisplatin nephrotoxicity.

• HIGH on days 1 and 29, with substantial risk for delayed emesis on days 2 through 4 and 30 through 32.
• Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
• Radiation therapy may induce clinically significant nausea and vomiting.
• Refer to UpToDate topics on radiotherapy-induced nausea and vomiting.

• Routine prophylaxis is not indicated.
• Refer to UpToDate topics on infusion reactions to systemic chemotherapy.

• Cisplatin is an irritant but can cause significant tissue damage; avoid extravasation.
• Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.

• Primary prophylaxis with G-CSF not warranted; the use of G-CSF with concurrent chemotherapy and radiotherapy should be avoided.^[3]
• Refer to UpToDate topics on locally advanced squamous cell carcinoma of the head and neck and use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.

• CBC with differential prior to each chemotherapy course.

• Assess electrolytes and liver and renal function prior to each chemotherapy course.

• Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.

• Assess change in neurologic function prior to each chemotherapy course.

• Monitor for diarrhea, stomatitis, and cutaneous toxicity during therapy (palmar-plantar erythrodysesthesias).

• Hold FU for grade 2 or greater diarrhea, and restart at a lower dose after resolution.
• NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for dihydropyrimidine dehydrogenase deficiency.
• Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.

• In the original protocol, radiotherapy, cisplatin, and FU were held for ANC <1000/microL and platelet count <75,000/microL on day 1 of cycle 2.^[4] Therapy was resumed when counts recovered to above these values, and FU was restarted at 80% of original dose (800 mg/m² per day). Chemotherapy was discontinued if counts did not recover after a seven-day period. For a nadir ANC <500/microL or platelet count <50,000/microL, the FU dose was reduced to 800 mg/m² per day for the next cycle of therapy.

• Hold cisplatin until serum creatinine is <1.5 mg/dL and/or blood urea nitrogen is <25 mg/dL. For grade ≥2 nephrotoxicity during treatment (creatinine >1.5 times normal value despite adequate hydration), creatinine clearance should be determined prior to next cycle. In the original protocol, for a calculated creatinine clearance 30 to 49 mL/min, the dose of cisplatin was reduced by 50% and cisplatin was discontinued for creatinine clearance <30 mL/min.^[4]

• In the original protocol, all therapy was held for grade 3 or 4 stomatitis, esophagitis, or dermatologic/skin reaction until resolution of toxicity to ≤grade 2 and the FU dose was decreased to 800 mg/m2 per day for the subsequent cycle.^[4] If chemotherapy could not be resumed within seven days, FU was discontinued.^[5]
• Refer to UpToDate topics on oral toxicity associated with chemotherapy and cutaneous complications of conventional chemotherapy agents.

• There is no recommended dose for resumption of FU administration following development of hyperammonemic encephalopathy, acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances; the drug should be permanently discontinued.^[5]

• Cardiotoxicity observed with FU includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes, and cardiomyopathy. There is no recommended dose for resumption of FU administration following development of cardiac toxicity, and the drug should be discontinued.^[5]