Phase I study of picoplatin and docetaxel (D) with prednisone (P) in patients (pts) with chemotherapy-naive metastatic hormone refractory prostate cancer (HRPC)

Abstract

15546 Background: Picoplatin is a sterically hindered platinum analogue specifically developed to overcome platinum resistance and to improve on the safety and efficacy of other platinum-based drugs. In >600 pts, picoplatin had single-agent activity in prostate, lung, ovarian and other malignancies with rare clinically significant nephro-, oto-, or neurotoxicity (∼2% grade 3 and 0% grade 4), even in platinum pretreated pts. An objective response rate of 20% and a PSA response rate of 25% were observed following 120 mg/m2 picoplatin q 3 wk in 20 chemotherapy-naïve pts with HRPC. D + P leads to superior survival, increased PSA response and improved quality of life in HRPC pts. Picoplatin has demonstrated synergy with taxanes in pre-clinical studies. Thus the current study is designed to investigate D + P + picoplatin in chemotherapy-naïve pts with metastatic HRPC. Methods: Pts with documented progression of metastatic disease during adequate hormonal therapy, ECOG performance status of 0 or 1 and preserved organ function received D, 60 mg/m2 q 3 wks + P, 5 mg, po bid + picoplatin. Picoplatin has been given to date to sequential cohorts of subjects at 60 mg/m2, 80 mg/m2 and 100 mg/m2. Results: 16 pts have been enrolled and have received up to 8 cycles of therapy. Therapy has been well tolerated. No dose limiting toxicity has been observed. Dose reduction for thrombocytopenia has been required in 1 pt, but there has been no cumulative myelotoxity. 7 pts in the first 3 dose cohorts have been evaluated for efficacy after 4 cycles (12 weeks): at doses below the maximum tolerated dose, there were 3 PSA responses and 1 objective partial response. Dose escalation continues. Conclusion: Picoplatin can be safely administered with D + P in chemo-naïve pts with HRPC. A phase 2 study of this combination will begin when an optimal, safe dose is defined. No significant financial relationships to disclose.