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.
Ajani
J A
JA
The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Mail Stop 426, Houston, Texas, 77030, USA. jajani@mdanderson.org
Safran
H
H
Bokemeyer
C
C
Shah
M A
MA
Lenz
H-J
HJ
Van Cutsem
E
E
Burris
H A
HA
Lebwohl
D
D
Mullaney
B
B
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