A phase II trial of epirubicin (E), estramustine phosphate (EP), and celecoxib (C) as second line treatment of patients (pts) with hormone resistant prostate cancer (HRPC)

Abstract

14567 Background: Celecoxib, epirubicin, and estramustine phosphate affect prostate cancer cells through different mechanisms. All three could be synergistic. We studied the effects of this combination on PSA, response, toxicity and survival in pts with HRPC. Methods: Pts after progression from first line taxane-based chemotherapy with rising PSA and radiographic progression were eligible. Treatment was E30 mg/m2 iv on day 1 and 8 of each 4 week cycle; EP 280 mg po bid daily × 3 days every wk × 2 followed by 2 wks rest; C 400 mg po bid daily for 28 days. All pts were assessed for response every 2 cycles. Dose modifications for hematologic and hepatorenal toxicity were made. RECIST criteria and PSA decline>50% were used to define response. Results: Sixteen pts enrolled, and 13 are evaluable for toxicity and response. Two withdrew before treatment and one for toxicity. The Median (M) age was 71.5 yrs (59–87), ECOG PS 1 (0–1), Gleason score 7 (4–9), LDH 172 (131–244), Hgb 11.1 (8.8–11.9), PSA 75 (6–814). Pts received M 4 cycles (2–10). Nine (69%) pts had soft tissue and 12 (92%) pts had bone metastases. For radiographic response, 11 pts were evaluable; 6 had stable disease and 2 had complete response by CT. Two pts had response by bone scan. Nine (69%) pts had PSA response. The M survival was 441 days (10–995). There were 5 SAE - DVT, diarrhea, bowel obstruction, cord compression and myocardial infarction. There was good renal and cardiac tolerance. Conclusions: This combination was safe and showed good and durable response as a second line regimen. [Table: see text]