A phase II study of patupilone in patients with metastatic hormone refractory prostate cancer (HRPC) who have progressed after docetaxel

Abstract

5166 Background: Reliably effective chemotherapy for patients (pts) with HRPC who have progressed after docetaxel remains to be identified. Patupilone is an epothilone with broad spectrum pre-clinical activity including in taxane resistant models. Methods: Multi-center, 2-stage design. Pts with metastatic HRPC with progressive disease documented within 6 months of or while receiving docetaxel were eligible. Patupilone was initially given 10 mg/m2 IV every 3 weeks. PSA response (≥50% decline from baseline) was the primary endpoint. Forty-three pts were to be accrued to stage 1 (H0: response rate <15%, H1: PSA response rate > 25%) and continue to stage 2 if > 6 responses seen. Secondary measures of outcome included progression free and overall survival, measurable disease response, and serial pain and analgesics scores. Results: To date, 33 pts have been enrolled with data available on 19 receiving a median of 4 cycles (range 1–7). Baseline characteristics (range): median age 66 (53–78), PSA 248 (17–1170), hemoglobin 114 (94–149), median time from last docetaxel 4.8 months (1.4–15.0), number of prior chemotherapy regimens 1:2:3+ in 5:10:4 pts, ECOG PS 0:1:2 in 3:12:4 pts, disease in bone, lymph nodes and viscera in 18, 13 and 4 pts respectively. Four first cycle gastrointestinal serious adverse events occurred in the first 6 pts (diarrhea and vomiting) and the dose of patupilone was lowered to 8 mg/m2 for subsequent patients with better tolerance. Grade 3/4 related adverse events at the 8 mg/m2 dose (13 pts): fatigue (1 pt), diarrhea (2 pts) and abdominal pain (1 pt). There have been no grade 3/4 hematologic adverse events. Thus far, PSA declines of ≥30% and ≥50% have occurred in 12/19 (63%) and 8/19 (42%) pts with a confirmed PSA response occurring in 5 pts (26%). Three pts (16%) have had PSA progression as best response. Of 8 pts with evaluable measurable disease, 7 (88%) have had stable disease and 1 pt has had progression as best response. Conclusions: In this population, patupilone 8 mg/m2 every 3 weeks is well tolerated. Initial results show encouraging PSA responses in pts with docetaxel resistant/refractory disease and accrual continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis