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

• Published in: Investigational new drugs Vol. 24; no. 5; pp. 441 - 446
• Main Authors: Ajani, J A, Safran, H, Bokemeyer, C, Shah, M A, Lenz, H-J, Van Cutsem, E, Burris, 3rd, H A, Lebwohl, D, Mullaney, B
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.09.2006
• Subjects: Adenocarcinoma - drug therapy; Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Bridged-Ring Compounds - therapeutic use; Cancer; Cancer therapies; Chemotherapy; Clinical trials; Disease Progression; Drug dosages; Drug therapy; Epothilones - administration & dosage; Epothilones - adverse effects; Epothilones - therapeutic use; Female; Gastric cancer; Gastrointestinal diseases; Hematology; Humans; Male; Metastasis; Middle Aged; Multicenter Studies as Topic; Oncology; Peripheral Nervous System Diseases - chemically induced; Pharmacology; Radiation therapy; Response rates; Schedules; Stomach Neoplasms - drug therapy; Surgery; Taxoids - therapeutic use; Toxicity
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-006-7304-8

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 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). 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. 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.