A Phase IIa trial of weekly EPO906 in patients with hormone-refractory prostate cancer (HPRC)

Abstract

4563 Background: Single-agent taxanes have demonstrated clinical activity in HPRC; however, the median duration of response is relatively short. The epothilone EPO906 is a potent microtubule stabilizer that is not a substrate for multidrug-resistance protein and has demonstrated clinical cytotoxic activity in taxane-sensitive, -resistant, and refractory tumors. Thus, EPO906 may be an appropriate alternative to taxane therapy in patients (pts) with HRPC. In a phase IIa study, we investigated the safety and efficacy of weekly EPO906 in these pts. Methods: Pts with histologically proven disease with documented metastases or prostate-specific antigen (PSA) progression > 20 ng/mL were enrolled. Pts could have received ≤ 1 prior chemotherapy regimen for hormone-resistant disease. Pts were maintained on androgen ablation therapy or had undergone an orchiectomy. EPO906 2.5 mg/m2 was administered via a 5-min IV infusion once weekly for 3 wks followed by 1 wk of rest for 6 cycles. Results: A total of 37 pts with a median age of 68 yrs (range, 52 - 82 yrs) were enrolled, 95% had a performance status of ≤ 1. Twenty-nine pts had received prior chemotherapy. Pts received a median of 3 cycles (range, 1 - 12) of EPO906. EPO906 was well tolerated; the most common adverse events were gastrointestinal. Grade (gr) 3 or 4 diarrhea, fatigue, dehydration, abdominal pain, and vomiting were reported in 7 (19%), 5 (14%), 3 (8%), 2 (5%), and 2 (5%) pts, respectively. Gr 2 diarrhea was reported in 7 (19%) pts. Gr 1 and 2 peripheral neuropathy was reported in 5 (14%) and 2 (5%) pts, respectively. Five pts withdrew because of adverse events, although only 1 pt discontinued for a clinically significant adverse event (gr 3 diarrhea). Gr ≤ 2 anemia was reported in 7 (19%) pts; there were no reports of neutropenia or thrombocytopenia of any grade. By PSA assessment, 8 (22%) had a PR, 6 (16%) had SD, and 16 (43%) had PD. PSA values were not available for 7 pts. By tumor assessment, there were 4 PR out of 20 pts with measurable disease. Two pts are ongoing. Conclusions: Weekly EPO906 was generally well tolerated and active in pretreated pts with HRPC. Future studies will determine the role of this agent in the treatment of prostate cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. ICPME; Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Genentech Novartis