A phase II study of picoplatin with docetaxel and prednisone in chemotherapy-naïve patients with metastatic hormone refractory prostate cancer (HRPC)

Abstract

5153 Background: Picoplatin(Pico) is a platinum therapy specifically designed to overcome platinum resistance and to improve safety and efficacy compared to other platinums. In HRPC, a PSA response rate of 25% was observed when picoplatin monotherapy was infused at 120 mg/m2 q3w (N = 20). A 34 pt Phase I study was performed to investigate the safety and efficacy of Pico in combination with docetaxel + prednisone (pred) in patients with metastatic HRPC. Picoplatin therapy was well-tolerated and19 of 32 evaluable pts (59%) achieved confirmed PSA responses. 120 mg/m2 Pico with docetaxel (D) 75 mg/m2 and pred, was determined to be the MTD and supported this dose level for the Phase II study to evaluate safety and efficacy of Pico with D and pred. Methods: Pts with HRPC with disease progression received Pico and D q3w with pred 5 mg po bid at dose levels of 75 mg/m2 D with 120 mg/m2 Pico for up to 10 cycles. PSA responses were evaluated in a manner consistent with the Bubley criteria. CT and bone scans are being evaluated. Results: 30 pts were enrolled and have received 1–10 cycles at this time. Of 22 pts currently evaluable for PSA response, 13 (59 %) achieved a PSA response, a >50% decrease in PSA maintained for at least 4 weeks. 9 pts have discontinued study treatment because of progressive disease and 2 due to SAEs unrelated to picoplatin. Combined safety data from Phase I and Phase II indicates the commonest adverse events are neutropenia, alopecia, thrombocytopenia, anemia and nausea. 12 pts have received >800 mg/m2. No neurotoxicity > grade 1 has been observed. Conclusions: Picoplatin at 120 mg/m2 can be safely administered with 75 mg/m2 docetaxel and prednisone. Preliminary PSA response data (59%) indicates potential improved efficacy of this novel combination in the treatment of patients with HRPC. Additional Phase II data is being evaluated in this study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Poniard Pharmaceuticals Poniard Pharmaceuticals