Phase II study of sagopilone (ZK-EPO) plus prednisone as first-line chemotherapy in patients with metastatic androgen-independent prostate cancer (AIPC)

Abstract

5141 Background: The microtubule stabilizer docetaxel, in combination with prednisone, prolongs life in patients with metastatic AIPC. Epothilones are a new class of microtubule stabilizers. The activity and safety of the fully synthetic epothilone B analogue sagopilone (ZK-EPO) was evaluated in chemotherapy-naïve AIPC patients. Methods: Patients with metastatic AIPC received sagopilone, 16 mg/m2 IV over 3 hours every 21 days and prednisone 5 mg PO BID continuously. Treatment was repeated every 21 days for up to 6 cycles. Extended treatment was allowed for patients felt to benefit from treatment at the end of 6 cycles. Among the first 13 patients, 3 responders (consensus PSA criteria) were required for enrollment to continue to a total goal of 46. Results: 29 patients were enrolled between August 2006 and October 2007 and accrual continues. All patients are evaluable for safety and 24 of 29 patients are evaluable for response. Patients who were not evaluable for response include 4 on treatment and 1 who was ineligible. The median number of cycles therapy was 4 (range 1 to 11). Toxicity ≥Grade 3 included: neuropathy 24%, fatigue 8%, diarrhea 4%, dizziness 4%. Of the 24 patients evaluable for response, 5 (21%; 95%CI: 7–42%) met the criteria for PSA response (confirmed ≥50% reduction in PSA) and 14 (58%; 95%CI: 37–78%) had a 30% reduction in PSA within 3 months of enrollment, a measure recently shown to most strongly correlate with subsequent survival in studies of docetaxel. Of 12 patients with radiographic measurable disease, 1 had a confirmed complete response and 1 a confirmed partial response (PR) by RECIST criteria. An additional 4 patients had an unconfirmed PR. Conclusions: Sagopilone is active in AIPC. Further follow-up is required to verify the level of activity and tolerability and to set this in the context of other agents, such as docetaxel combined with prednisone. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Oncology Bayer HealthCare Pharmaceuticals Bayer HealthCare