Multi-institutional trial of the epothilone B analogue BMS-247550 with or without estramustine phosphate (EMP) in patients with progressive castrate-metastatic prostate cancer (PCMPC): Updated results

Abstract

4509 Background: BMS-247550 is a semi-synthetic analogue of epothilone B with preclinical activity in taxane-resistant cell lines. We have previously shown that BMS-247550 + EMP could be safely administered in PCMPC (Ann Oncol 14:1518, 2003). Subsequently, we initiated a multi-institutional phase II study to determine the efficacy and toxicity of BMS-247550 +/- EMP. Methods: Chemotherapy-naïve patients with PCMPC were eligible. Patients were randomized to BE: BMS-247550 (35 mg/m2 IV over 3 hours every 3 weeks on day 2) + EMP (280 mg PO TID day 1–5) + Coumadin (2 mg daily) or B: BMS-247550 (35 mg/m2 IV over 3 hours every 3 weeks). Results: Accrual has completed with 92 patients enrolled (BE: 45, B: 47). Patients have received a median of 5 cycles (range, 1–12) on BE and 4 cycles (range, 1–25) on B. Twenty-two patients continue on treatment. The major adverse events are detailed in the table. Neuropathy developed after a median of 3 cycles (range, 1–7). On BE, 22/32 (69%; 95% CI, 53–85%) have achieved a ≥ 50% decline in PSA and 8/18 (44%; 95% CI, 21–69%) have had a partial regression (PR) of measurable disease. On B, 18/32 (56%; 95% CI, 39–73%) have achieved a ≥ 50% decline in PSA and 6/26 (23%; 95% CI, 7–40%) have had a PR. At a median follow-up of 6.5 months (range, 0–23), 81 patients are alive and 11 have died. Conclusions: BMS-247550, alone or in combination with EMP, has significant activity in PCMPC. Neuropathy is prominent, has proven manageable, yet requires further characterization. Phase III studies are needed to determine if BMS-247550 confers a survival benefit. Support: CTEP, Prostate Cancer Foundation, NIH N01-CM17105 Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb; Cell Therapeutics; Pfizer Cell Therapeutics AstraZeneca Speakers Bureau Aventis; AstraZeneca; Prostate Cancer Foundation; Millennium Pharmaceuticals ProQuest Investments ProQuest Investments