A phase II trial of docetaxel plus carboplatin in hormone refractory prostate cancer (HRPC) patients who have progressed after prior docetaxel chemotherapy: Preliminary results

Abstract

14533 Background: Treatment options for HRPC patients who progress after docetaxel chemotherapy are limited. Carboplatin may enhance the efficacy of docetaxel chemotherapy. Methods: We prospectively treated HRPC patients with documented PSA or radiographic progression during a minimum of 2 cycles of docetaxel-based chemotherapy or within 45 days of completing therapy. No prior platinum was allowed, though patients may have received other prior chemotherapy. Patients received docetaxel 60 mg/m2 and carboplatin AUC (4) every 21 days until progression or unacceptable toxicity. Measurable response was assessed by RECIST criteria. PSA declines were assessed per PSA Working Group; 2 patients were not evaluable as they received only 1 cycle of therapy but are included in the denominator. Results: Interim data is available on the 1st stage of patients (n = 16) enrolled in this ongoing phase II trial. Median age was 69 years (range 46–81), 94% white. Baseline performance status was 0 or 1 in 88%. Prior therapies included antiandrogens (80%) and ketoconazole (47%); docetaxel was used alone (33%), with estramustine (33%) or another agent (33%). Median PSA at baseline was 44 ng/ml (range 4.9–4801). Patients received a median of 3 cycles of docetaxel/carboplatin (range 1–12+). PSA declines of ≥50% were noted in 3 of 16 patients (19%, 90% C.I. 5–42%). In addition, 5 patients had SD, suggesting clinical benefit in 50% (90% C.I. 28–72%). Of 10 patients with measurable disease at baseline, 2 (20%; 90% C.I. 4–51%) had confirmed PR. Therapy was well-tolerated, with no treatment-related deaths and five grade 3 toxicities, including anemia (1), leukopenia (3) and hyperglycemia (1). Median time to progression was 2.7 months (range 0–13.4); median survival was 11.7 months (95% C.I. 6.7–14.0). Conclusions: In preliminary analyses, docetaxel plus carboplatin demonstrated encouraging activity in patients who progressed after docetaxel-based therapy. PSA declines ≥50% were seen in 19%; measurable responses in 20%. Accrual is ongoing. Final analyses will include correlation of response to serum markers of neuroendocrine differentiation. (Supported by BMS). No significant financial relationships to disclose.