A multi-center phase II study of BMS-247550 (Ixabepilone) by two schedules in patients with metastatic gastric adenocarcinoma previously treated with a taxane
Ajani, J A × Safran, H Bokemeyer, C Shah, M A Lenz, H-J Van Cutsem, Eric Burris, H A Lebwohl, D Mullaney, B #
Investigational new drugs vol:24 issue:5 pages:441-6
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, > or =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/m2 every 21 days (23 patients; cohort A) and 24 subsequent patients were treated with an amended protocol schedule to receive 6 mg/m2 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.