Results of a phase II study of picoplatin with docetaxel and prednisone in first-line treatment of castration-resistant prostate cancer (CRPC)

Abstract

5140 Background: Picoplatin (Pico) was designed to overcome platinum resistance and has the potential for improved safety compared to other platinum agents. Previously, a PSA response rate of 25% was observed when Pico monotherapy was infused at 120 mg/m2 Q3W (N = 20). Recently, a 34-patient Phase I study was performed to investigate the safety and efficacy of Pico in combination with docetaxel (D) + prednisone (pred) as first-line therapy for metastatic CRPC. Picoplatin therapy was well-tolerated at a dose of 120 mg/m2 and 19 of 32 evaluable pts (59%) achieved a confirmed PSA response. Methods: 32 patients with chemotherapy-naïve CRPC and disease progression received Pico (120 mg/m2) and D (75 mg/m2) Q3W with pred 5 mg po bid for up to 10 cycles. PSA responses were defined as a reduction from baseline of at least 50% maintained for at least 4 weeks. CT and bone scans were also evaluated. Tumor response was measured using RECIST. Results: Patients received a median of 10 cycles (range = 1–10). Median baseline PSA was 340.8 ng/mL (range 5.6–3019). One pt had no baseline PSA data. Of the 24 patients with evaluable post-treatment PSA, 83% (95% CI 64–93%) had PSA decreases <50% of baseline, and in 8 of these (33% of the evaluable population), PSA reached normal levels (< 4 ng/mL). In the intent-to-treat population, the PSA response rate was 63% (95% CI 45–77%). 13 patients evaluated by CT scan had measurable disease; 6 pts had SD by RECIST, 4 had PD, and 3 were not evaluable. The most common adverse events were alopecia (36%), asthenia (32%), neutropenia (29%), increased creatinine (23%), and thrombocytopenia (19%). No neurotoxicity ≥ grade 2 was observed. Conclusions: Picoplatin was safely administered to patients with CRPC as 1st-line therapy at 120 mg/m2 Q3W with full doses of docetaxel and prednisone, resulting in a PSA response rate of 83% of evaluable patients. These results support further development of picoplatin as a novel combination with docetaxel for the treatment of CRPC. [Table: see text]