Phase I trial of oxaliplatin in combination with cisplatin, protacted-infusion fluorouracil, and radiotherapy in advanced esophageal and gastroesophageal carcinoma

PURPOSE: To define the maximum-tolerated dose of oxaliplatin given with cisplatin, protacted 96-h infusion of fluorouracil, and radiotherapy for patients with advanced esophageal cancer. PATIENTS AND METHODS: Seventeen patients with locally advanced esophageal cancer and 2 patients with local recurrence were treated. Escalating doses of oxaliplatin, cisplatin, and fluorouracil were administered on Days 1 and 29 of radiotherapy. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy. Dose-limiting toxicity was defined as a Grade 4 hematologic or Grade 3-4 nonhematologic toxicity. RESULTS: Dose-limiting toxicity caused by diarrhea and asthenia was observed at the IV level. The recommended dose was 85 mg/m- oxaliplatin, 55 mg/m2 cisplatin, and 3000 mg/m2 96-h fluorouracil infusion. Two pathologic complete responses were observed in 12 patients selected for surgery (16%). CONCLUSIONS: Oxaliplatin, cisplatin, fluouracil, and radiotherapy can be administered together with acceptable toxicity. A Phase II trial is ongoing with resectable esophageal and gastric carcinoma.