Phase II trial of oxaliplatin, leucovorin and fluorouracil in patients with advanced carcinoma of the esophagus

Background: The aim of the study was to evaluate the efficacy and tolerability of the combination of oxaliplatin, fluorouracil and leucovorin in patients with advanced esophagus cancer. Patients and methods: Thirty-five patients with recurrent or metastatic esophageal adenocarcinoma or squamous cell carcinoma were enrolled. Up to one prior chemotherapy regimen was allowed. All patients had bi-dimensionally measurable disease. Patients received oxaliplatin 85mg/m2 as a 2-h infusion on day 1. Leucovorin (500mg/m2) followed by fluorouracil bolus (400mg/m2) and 22-h continuous infusion fluorouracil (600mg/m2) was administered on days 1 and 2. Granulocyte colony stimulating factor was not routinely administered unless the patient developed febrile neutropenia or prolonged neutropenia. Treatment was repeated every 14 days. Results: Of the thirty-five patients enrolled, all were evaluated for toxicity and 34 were evaluated for response. The overall response rate was 40% (95% confidence interval, 24% to 57%) with complete and partial response rates of 3% and 37%, respectively. The median response duration was 4.6 months, and the median overall survival was 7.1 months. One-year survival was 31%. The major toxicity noted was cumulative neutropenia, with 29% developing grade 4 toxicity. There was one treatment-related death secondary to neutropenic sepsis. The most common non-hematologic toxicity encountered with this regimen was cumulative peripheral neuropathy, with 26% experiencing grade 2 or 3 toxicity. Conclusions: The combination of oxaliplatin, leucovorin, and fluorouracil shows significant anti-tumor activity and a favorable toxicity profile in patients with metastatic carcinoma of the esophagus.