Granulocyte macrophage: Colony stimulating factor (GM-CSF), ketoconazole, and mitoxantrone as second-line therapy in patients (Pts) with progressive hormone refractory prostate cancer (HRPC)

Abstract

e16033 Background: A variety of docetaxel regimens have been tested in HRPC pts, yielding response rates between 38% - 69%. Docetaxel therapy has been widely used as first line therapy. Second line therapies, which are non - taxane based with comparable activities do not exist. This trial is built on the significant body of work which has demonstrated anti-tumor activity of GM-CSF, Ketoconazole and Mitoxantrone alone and in combination in pts with HRPC. The trial is designed to assess the combination of all three agents. Methods: No more than two prior chemotherapy regimens (one which contained docetaxel), progressive disease, and adequate marrow / organ function. Treatment consisted of: Ketoconazole daily 400mg po tid, GM-CSF subcutaneous 250mcg / m2 (14 days on/ 7 days off) and Mitoxantrone 12mg / m2 every 3 weeks (maximum cumulative dose of 140mg / m2), until either the completion of Mitoxantrone or maximum anti-tumor benefit. Pts continued Ketoconazole/ GM-CSF until disease progression. PSA was evaluated every 3 weeks and radiographic studies were performed every 9 weeks. Results: 31 pts were enrolled; 4 pts with PSA only, 9 bone only, 5 soft tissue only, and 13 bone and soft tissue. 2 pts withdrew from study due to toxicity. 8 pts had a PSA response of ≥ 50%, 5 pts had a PSA response of ≥ 80%, and 7 pts had a PSA response of ≥ 90%. 9 pts progressed. The majority of pts had stabilization of their bone and soft tissue involvement and 2 pts with nodal involvement demonstrated a radiographic CR. Significant adverse events included grade III/IV neutropenia, thrombocytopenia, and nausea. Median duration of treatment was 6.22 months (range 2 months - 20.5 months). Conclusions: GM-CSF, Ketoconazole and Mitoxantrone in combination demonstrate significant anti-tumor activity and reversible toxicity in pts who have failed prior docetaxel therapy. Information regarding PSA response, radiographic outcome and adverse event data will be presented. This data warrants further investigation such as a randomized phase II study. [Table: see text]