Annals of Oncology 15:928-932, 2004
© 2004 European Society for Medical Oncology
Original Paper |
A phase II trial of the epothilone B analog, BMS-247550, in patients with previously treated advanced colorectal cancer
Received 17 February 2004; revised 25 February 2004; accepted 26 February 2004Background:
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).
Patients and 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 
1; peripheral neuropathy grade 1; and adequate laboratory parameters. BMS-247550 40 mg/m2 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/m2) administered every 21 days demonstrated no activity in advanced colorectal cancer. Peripheral neuropathy was treatment-limiting.
1 Department of Medicine, Section of Hematology/Oncology and 2 Department of Health Studies, University of Chicago, Chicago, IL; 3 Fort Wayne Medical Center, Fort Wayne, IN; 4 Northern Indiana Cancer Research Consortium, South Bend, IN, USA
Key words: colorectal cancer, epothilone, phase II trial
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