Diethylstilbestrol and docetaxel: A phase II study in patients with metastatic, androgen independent prostate cancer.

4739 Background: The combination of diethylstilbestrol (DES) and docetaxel has additive to synergistic activity against prostate cancer in preclinical models and DES inhibits expression of taxane resistant tubulin isoforms. In an ongoing phase II trial we determined the effects of the combination of DES and docetaxel on PSA, overall response, and toxicity.,Thirteen pts with metastatic androgen independent prostate cancer progressing by rising PSA or scan were treated with DES 5 mg po qd the day prior to docetaxel and 1 mg po qd continuously in combination with Docetaxel 36mg/m2 IV over 30 min,weekly for 3 weeks of a 4 week cycle. All pts were assessed by PSA monthly and radiological tests every 3 cycles. Dose modifications for hematologic, hepatic and renal toxicity were made. The RECIST criteria and PSA decline by >50% which was maintained for 4 weeks were used.,The median age was 65 years (58-82), SWOG PS 1(0-1), alkaline phosphatase 170 U/L (71-523), Hgb 12.0 g/dL (9.2-13.9), PSA 87 ng/dL (4.15-386). To date the median number of cycles was 6 and therapy is ongoing in the majority of patients. The median follow up is 6 mos (3-18). Soft tissue metastases were present in 6 pts (46%) and bone metastases in 13 pts (100%). Thirteen pts are evaluable for response. Of these, 9 pts (69%) had PSA responses and the PSA declined by > 90% in 6 pts (46%). The overall response for 13 pts was 77%. 2 pts (18.2%) had grade III diarrhea. One patient died of causes unrelated to therapy.,The combination of DES and docetaxel is very well tolerated and toxicity is indistinguishable from docetaxel alone. The overall response rate was 77% in a limited number of patients, suggesting that DES improves the therapeutic index of docetaxel when used in a weekly regimen. PSA decline by>50% and substantially greater PSA declines, soft tissue, and bone scan responses were demonstrated. Further accrual and longer follow up will determine its full significance in pts with androgen independent prostate cancer. (Supported by Sanofi Aventis). [Table: see text].