A multi-center phase II study of BMS-247550 (Ixabepilone) by two schedules in patients with metastatic gastric adenocarcinoma previously treated with a taxane Journal Article
| Authors: | Ajani, J. A.; Safran, H.; Bokemeyer, C.; Shah, M. A.; Lenz, H. J.; Van Cutsem, E.; Burris, H. A. 3rd; Lebwohl, D.; Mullaney, B. |
| Article Title: | A multi-center phase II study of BMS-247550 (Ixabepilone) by two schedules in patients with metastatic gastric adenocarcinoma previously treated with a taxane |
| Abstract: | 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/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. © Springer Science + Business Media, LLC 2006. |
| Keywords: | adult; clinical article; controlled study; human tissue; treatment response; aged; middle aged; clinical trial; constipation; drug activity; fatigue; neutropenia; diarrhea; drug safety; skin toxicity; antineoplastic agents; skin manifestation; antineoplastic agent; anorexia; adenocarcinoma; metastasis; controlled clinical trial; drug eruption; liver toxicity; nephrotoxicity; phase 2 clinical trial; sensory neuropathy; blood toxicity; esophagitis; gastrointestinal symptom; nausea; stomatitis; dehydration; myalgia; cohort analysis; bone pain; histology; abdominal pain; arthralgia; drug hypersensitivity; dyspnea; febrile neutropenia; confidence interval; chemotherapy induced emesis; dysphagia; odynophagia; disease progression; multicenter study; drug response; muscle weakness; taxoids; dermatitis; taxane derivative; informed consent; stomach adenocarcinoma; urogenital tract disease; alopecia; neurologic disease; neuropathic pain; stomach neoplasms; abdominal cramp; esophagus carcinoma; allergic reaction; musculoskeletal disease; peripheral nervous system diseases; granulocytopenia; lower esophagus sphincter; bone marrow toxicity; ixabepilone; epothilones; electrocorticography; bridged compounds; pharyngitis; multicenter studies; neutrophilia |
| Journal Title: | Investigational New Drugs |
| Volume: | 24 |
| Issue: | 5 |
| ISSN: | 0167-6997 |
| Publisher: | Springer |
| Date Published: | 2006-09-01 |
| Start Page: | 441 |
| End Page: | 446 |
| Language: | English |
| DOI: | 10.1007/s10637-006-7304-8 |
| PUBMED: | 16586011 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 29" - "Export Date: 4 June 2012" - "CODEN: INNDD" - "Source: Scopus" |
