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


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.
The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Mail Stop 426, Houston, Texas, 77030, USA. jajani@mdanderson.org
J A
JA
Ajani
H
H
Safran
C
C
Bokemeyer
M A
MA
Shah
H-J
HJ
Lenz
E
E
Van Cutsem
H A
HA
Burris
D
D
Lebwohl
B
B
Mullaney
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D018450:Disease Progression; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D013274:Stomach Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D034261:Epothilones; D043823:Taxoids; C080625:taxane; C430592:ixabepilone