Phase II Trial of Continuous Infusion Carboplatin, 5-Fluorouracil, and Radiotherapy for Localized Cancer of the Esophagus

The aim of this study was to determine the toxicity, response rate, failure-free survival, and overall survival in a treatment program comprising continuous infusion carboplatin, short in-fusion 5-fluorouracil (5-FU) and radiotherapy for localized carcinoma of the thoracic esophagus. To be eligible, patients were required to have Karnofsky performance status greater than or equal to 60, adequate organ function, and have received no prior therapy. Planned radiation dose was 50 Gy in 25 fractions over 5 weeks. 5-FU was to be administered commencing days 1 and 29 of radiotherapy, and given at a dose of 1 g/m2/d for 4 days as a continuous infusion. Carboplatin was to commence on day 1 of radiotherapy and be given throughout the period of radiation as a continuous infusion. The starting dose of carboplatin was 28 mg/m2/d. The protocol specified a 25% dose reduction of carboplatin if more than two of the first six patients experienced dose-limiting toxicity (DLT). DLT was defined as grade IV neutropenia lasting more than 7 days, grade IV thrombocytopenia, or any grade IV nonhematologic toxicity. All 23 patients in the study received protocol radio-therapy, except one who was given an extra 10 Gy. Seven patients received carboplatin at 28 mg/m2/d and 16 received 21 mg/m2/d. Hematologic DLTs were experienced by all of the seven patients receiving the higher dose. No patients in the low-dose group experienced hematologic DLTs, and only 2 of 16 ceased chemotherapy early because of myelosuppression. Three patients in the low-dose group experienced grade IV esophagitis but were able to complete protocol radiotherapy. Apart from esophagitis, nonhematologic toxicity was generally moderate or mild. Six patients had thrombosis complicating the central venous catheters. Endoscopy was performed in 21 patients (91%), with an overall complete response rate of 65% (CI: 43–84%) for the whole group or 71% (CI: 48–89%) for the endoscopically evaluated group. Estimated median failure-free survival time was 8.9 months (CI: 7.1–12.9), and estimated median overall survival time was 21.4 months (CI: 9.6 –35.4). Carboplatin at 21 mg/m2/d as a continuous infusion may be given safely in combination with short infusional 5-FU and radiotherapy for localized carcinoma of the esophagus. This combination has resulted in response data comparable to that of larger studies of cisplatin-containing regimens and warrants further study, ideally in a phase III randomized controlled trial.