A PHASE-II TRIAL OF INTERFERON-ALPHA 2A, 5-FLUOROURACIL, AND CISPLATIN IN PATIENTS WITH ADVANCED ESOPHAGEAL-CARCINOMA

Background, The combination of 5-fluorouracil (5-FU) and cisplatin has moderate antitumor activity in the treatment of metastatic epidermoid carcinoma of the esophagus. The authors have recently shown activity for the combination of 5-FU and interferon-alpha 2a (IFN-alpha) in both esophageal epidermoid and adenocarcinoma. A Phase II trial, therefore, was undertaken to evaluate the antitumor activity of the three-drug combination of IFN-alpha, 5-FU, and cisplatin in unresectable or metastatic esophageal carcinoma. Methods. Twenty-seven patients with locally advanced or metastatic carcinoma of the esophagus were treated, No prior chemotherapy was allowed. Twelve patients had epidermoid carcinoma (44%) and 15 patients had adenocarcinoma (56%), Patients received IFN-alpha at a dose of 3 X 10(6) units/day given daily by subcutaneous injection on days 1 to 28, 5-FU at a dose of 750 mg/m(2)/day for 5 days by continuous intravenous infusion on days 1 to 5, and cisplatin at a dose of 100 mg/m(2) on day 1. Treatment was recycled every 28 days, and after the first three cycles, cisplatin was administered only on alternate cycles. Twenty-seven patients completed a median of 4 cycles (range, 1-13 cycles), and 26 patients were evaluable for response. Results, Major responses were observed in 13 patients (50%, 95% confidence intervals, 31-69%), including two complete responses (8%). The response proportion in epidermoid carcinoma (8 of 11 patients, 73%) was higher than the response proportion in adenocarcinoma (5 of 15 patients, 33%). The median duration of response was 29 weeks (range, 11-74 weeks), similar in epidermoid carcinoma and adenocarcinoma, Toxicity was moderately severe but manageable with dose attenuations. Grade 3/4 hematologic toxicity was observed in 41% of patients and grade 3/4 nonhematologic toxicity was observed in 26% of patients. IFN-alpha was reduced to either a 3- or 5-day a week schedule because of fatigue and/or myelosuppression in 12 patients (44%). There were two treatment-related deaths (7%). Conclusions. In this Phase II trial, the combination of IFN-alpha, 5-FU, and cisplatin had substantial antitumor activity in esophageal carcinoma with apparently greater antitumor activity in epidermoid carcinoma than adenocarcinoma. A larger confirmatory trial comparing this treatment to conventional 5-FU and cisplatin is warranted for epidermoid carcinoma. In future chemotherapy trials, the response assessment for epidermoid and adenocarcinoma should continue to be stratified.