A phase I and II trial of epirubicin, cisplatin, 24-hour infusion 5 fluorouracil and sodium folinate in patients with advanced esophagogastric carcinomas

Aim: Advanced esophagogastric carcinoma has a poor prognosis. Palliative chemotherapy provides a survival advantage and improved quality of life. Epirubicin, cisplatin and continuous infusional 5-fluorouracil (5-FU) (ECF) is a well-established chemotherapy regimen but a continuous chemotherapy infusion is not always feasible or acceptable.Methods: We conducted a phase I and II trial of a modified version of ECF, utilizing 5-FU as a 24-h infusion on day 1 and day 8 of a 21-day cycle, administered with sodium folinate as a modulator of 5-FU (ECSF). In the phase I study the dose of 5-FU was increased in successive cohorts from 1250mg/m², 1500mg/m², and 1750mg/m² to 2000mg/m² per 24h.Results: Dose limiting toxicity of febrile neutropenia was encountered at 2000mg/m. The recommended dose for 5-FU was 1750mg/m². Overall 29 patients were treated with ECSF of whom 27 were evaluable for toxicity. The response rate was 45% on an intention-to-treat analysis with a complete response rate of 3%. The median response rate was 4.1months and the median survival was 10.7months. A total of 23 patients (72%) obtained clinical benefit with improvement in dysphagia or weight gain. central venous catheter (CVC) complications were observed in 12 (41%) patients.Conclusion: ECSF was associated with a response rate and survival similar to that reported with standard ECF. ECSF may provide an alternative regimen to standard ECF when a continuous ambulatory infusion pump is not feasible or not preferred by the patient. CVC complications are a limitation.