A phase II trial of the epothilone B analog, BMS-247550, in patients with previously treated advanced colorectal cancer.
BACKGROUND
The epothilone B analog, BMS-247550, is a non-taxane microtubulin-stabilizing agent with preclinical activity in taxane-resistant cell lines and phase I activity in colorectal cancer. We conducted a phase II study of single-agent BMS-247550 in advanced colorectal cancer patients who had disease progression following treatment with irinotecan-5-fluorouracil-leucovorin (IFL).


METHODS
Patients were required to have histologically or cytologically confirmed advanced or metastatic colorectal cancer; progressed on or after chemotherapy with IFL; Eastern Cooperative Oncology Group performance status < or =1; peripheral neuropathy grade < or =1; and adequate laboratory parameters. BMS-247550 40 mg/m(2) was administered intravenously over 3 h every 3 weeks. Patients were evaluated for response every 6 weeks.


RESULTS
Twenty-five patients were enrolled; all were evaluable for toxicity and 23 were evaluable for response. There were no complete or partial responses. Thirteen patients (56%) had stable disease after two cycles of therapy; five patients (20%) received six or more cycles. The median time to progression was 11 weeks; median overall survival was 36 weeks. There was considerable grade 3/4 hematological toxicity, including neutropenia (48%) and leukopenia (36%). Grade 3/4 non-hematological toxicities included grade 3 hypersensitivity reaction (12%) and peripheral neuropathy (20%).


CONCLUSIONS
Single-agent BMS-247550 (40 mg/m(2)) administered every 21 days demonstrated no activity in advanced colorectal cancer. Peripheral neuropathy was treatment-limiting.
Eng
C
C
Department of Medicine, Section of Hematology/Oncology, University of Chicago, IL 60612, USA. ceng@mdanderson.org
Kindler
H L
HL
Nattam
S
S
Ansari
R H
RH
Kasza
K
K
Wade-Oliver
K
K
Vokes
E E
EE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D034261:Epothilones / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017211:Treatment Failure
D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin