A Phase I Trial of 5-Fluorouracil with Cisplatin and Concurrent Standard-dose Radiotherapy in Japanese Patients with Stage II/III Esophageal Cancer

Abstract

In Japan, 5-fluorouracil (5-FU) 400 mg/m(2) on Days 1-5, 8-12, 36-40 and 43-46 with cisplatin (CDDP) 40 mg/m(2) on Days 1, 8, 36 and 43 plus concurrent radiotherapy with 2 weeks planned interruption (60 Gy) was standard for the patients with esophageal cancer. This Phase I trial was designed to determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of 5-FU on Days 1-4 and 29-32 with CDDP on Days 1 and 29 plus concurrent radiotherapy (50.4 Gy) among the Japanese. Escalating doses of 5-FU and CDDP were administered with concurrent radiotherapy (50.4 Gy). Treatment was continued until DLT appeared. Twelve patients with previously untreated clinical Stage II/III squamous cell esophageal carcinoma were studied. One of six patients given Level 1 (5-FU 800 mg/m(2) on Days 1-4 and 29-32 with CDDP 75 mg/m(2) on Days 1 and 29) developed a DLT of incomplete protocol treatment due to Grade 3 esophagitis. The MTD was not reached at Level 2 (5-FU 1000 mg/m(2) with CDDP 75 mg/m(2)). The complete response rate was 67% at Level 1 and 100% at Level 2. Dose Level 2 with 50.4 Gy radiotherapy was recommended for Japanese patients.