Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma

Background: Based on the observation of topoisomerase-1, upregulation by mitomycin C (MMC), and the phase I antitumor activity of sequential MMC/irinotecan in esophageal cancer, we conducted a phase II evaluation of two schedules of this combination in previously untreated stage III/IV esophageal/gastroesophageal junction adenocarcinomas. Patients and Methods: Patients (n = 76) were randomized to either 6 mg/m² MMC on day 1 and 125 mg/m² irinotecan on days 2 and 9 (arm A) or 3 mg/m² MMC on days 1 and 8 and 125 mg/m irinotecan on days 2 and 9 (arm B). Each cycle was repeated every 28 days. Restaging was planned after two cycles, and resections were performed whenever possible. A two-stage Simon minimax design was used for each arm, with a "pick-the-winner" approach based on efficacy. Results: The response rate (complete response + partial response) in 73 evaluable patients was 52% (21 of 40 patients) for arm A and 33% (11/33) for arm B. Moderate or severe toxicity was similar. Twenty-seven patients were resected (20:7, arm A:B). There was one complete pathologic response; five others were node negative. Conclusion: Irinotecan/MMC is feasible in esophageal/gastroesophageal junction adenocarcinoma. MMC (6 mg/m) every 28 days for up to six cycles is the recommended modulatory dose for irinotecan in future trials.