Annals of Oncology 14:1518-1524, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Pilot study of epothilone B analog (BMS-247550) and estramustine phosphate in patients with progressive metastatic prostate cancer following castration
1 Department of Medicine, 2 Department of Nursing and 3 Radiology, Genitourinary Oncology Service, Division of Solid Tumor, Memorial Sloan-Kettering Cancer Center, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY, USA
Received 10 February 2003; revised 24 April 2003; accepted 17 June 2003
Background:
Several trials have demonstrated that the response proportions to microtubule agents in patients with prostate cancer are increased by the addition of estramustine phosphate (EMP). The epothilone B analog BMS-247550 is a novel microtubule agent that has shown activity in taxane-resistant tumors. We conducted a dose-escalation study to determine a safe dose of BMS-247550 to combine with EMP in patients with metastatic prostate cancer.
Patients and methods:
Chemotherapy-naive patients with castrate-metastatic prostate cancer were treated with intravenous BMS-247550 and oral EMP (280 mg three times daily for 5 days) every 3 weeks.
Results:
Thirteen patients were treated at two dose levels (35 and 40 mg/m2). Three of six patients treated at 40 mg/m2 developed grade 4 neutropenia, establishing 35 mg/m2 as the maximum-tolerated dose. Significant peripheral neuropathy (grade 
2) was related to dose level and infusion rate. A decline in prostate-specific antigen (PSA) of 50% was seen in 11 of 12 evaluable patients (92%) (95% confidence interval 76% to 100%). There were objective responses in soft tissue (57%) and bone metastasis (40%).
Conclusions:
The phase II dose of BMS-247550 combined with EMP is 35 mg/m2 over 3 h every 3 weeks. This combination is safe and 50% post-therapy declines in PSA were seen in 11 of 12 patients (92%).
Key words: clinical trial, epothilone, estramustine phosphate, prostatic neoplasms
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