A multi-center phase II study of BMS-247550 (Ixabepilone) by two schedules in patients with metastatic gastric adenocarcinoma previously treated with a taxane

Purpose: Ixabepilone is one of the epothilones, a new class of cytotoxics, that function as microtubule-stabilizing agents. With the primary endpoint of assessing ixabepilone's response rate against metastatic gastric cancer previously treated with a taxane, we performed a multi-center phase II trial.Patients and methods: Patients with histologically documented metastatic gastric or gastroesophageal adenocarcinoma, who had previously received a taxane, were eligible. Patients were required to have near normal organ function, >= 18 years of age, ECOG performance status of 0 or 1. A written informed consent was obtained from all patients. Ixabepilone was administered over one hour intravenously at a dose of 50 mg/m(2) every 21 days (23 patients; cohort A) and 24 subsequent patients were treated with an amended protocol schedule to receive 6 mg/m(2) intravenously on days 1-5 every 21 days (cohort B).Results: A total of 47 patients were treated. Most patients were men with a median performance status of 1. Two of 23 patients in cohort A achieved a confirmed partial response (9%, 95% CI 1.1-28%) but none of the 24 patients in cohort B achieved a response. A higher proportion of patients in cohort A experienced Grade 3/4 toxicities compared with those in cohort B.Conclusions: Ixabepilone, on a once every 21-day schedule, is modestly active against metastatic gastric cancer previously treated with a taxane. The days 1-5 every 21 days schedule had a more favorable safety profile but no activity. The results of this study suggest that once every 21-day ixabepilone schedule should be pursued further in untreated gastric or gastroesophageal adenocarcinoma patients.