Low-dose continuous oral fosfestrol is highly active in 'hormone-refractory' prostate cancer

Background: Although not clearly defined, 'hormone refractory' prostate can cer implies disease progression after orchiectomy +/- antiandrogens. Patien ts in this setting are usually offered chemotherapy protocols which often l ead to significant toxicity and expense. In search of a well-tolerated, act ive, third-line treatment, we have attempted to prolong hormonal maneuvers by using low-dose estrogen therapy. Design: Thirty-eight patients with evidence of disease progression (as indi cated by 2 consecutively rising PSA determinations) after greater than or e qual to 2 hormonal treatments (including surgical or chemical orchiectomy a nd a median of 3 prior treatment lines) received fosfestrol 100 mg t.i.d. p er os in a continuous schedule until the appearance of progressive disease or excessive toxicity. Response was assessed by serial PSA levels. Complete response (CR) was defined as normalisation and partial response (PR) as a greater than or equal to 50 decrease of PSA levels for longer than one mont h. The median duration of prior treatment was 20 months and the median PSA at fosfestrol start was 126 ng/ml (range 8-12,800); symptoms (pain) were pr esent in 73% of patients. Results: CR + PR were observed in 79% (95% confidence interval: 66%-92%). T he median time to progression was seven months. Pain remained stable or imp roved in 34% and 53%, respectively, of symptomatic patients with PSA respon se. Toxicity included worsening of gynecomastia, peripheral edema, and deep vein thrombosis (8%). No treatment-related deaths occurred. Uni- and multi variate analyses failed to identify predictive factors for response. PSA re sponse was associated with significanly longer survival (13 vs. 7 months, P < 0.05 by Mantel-Haentzel). Conclusions: FOSF produces high rates of PSA-determined and symptomatic res ponse in 'hormone-refractory' prostate cancer. Toxicity and ease of adminis tration compare favorably with those reported for CHT regimens used in this setting. The role of estrogens in prostate cancer should be redefined.