BACKGROUND: Although not clearly defined, 'hormone refractory' prostate cancer implies disease progression after orchiectomy +/- antiandrogens. Patients in this setting are usually offered chemotherapy protocols which often lead to significant toxicity and expense. In search of a well-tolerated, active, 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 indicated by 2 consecutively rising PSA determinations) after > or = 2 hormonal treatments (including surgical or chemical orchiectomy and a median of 3 prior treatment lines) received fosfestrol 100 mg t.i.d. per 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 > or = 50 decrease of PSA levels for longer than one month. 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 present in 73% of patients. RESULTS: CR + PR were observed in 79% (95% confidence interval: 66%-92%). The median time to progression was seven months. Pain remained stable or improved in 34% and 53%, respectively, of symptomatic patients with PSA response. Toxicity included worsening of gynecomastia, peripheral edema, and deep vein thrombosis (8%). No treatment-related deaths occurred. Uni- and multivariate analyses failed to identify predictive factors for response. PSA response was associated with significantly longer survival (13 vs. 7 months, P < 0.05 by Mantel-Haentzel). CONCLUSIONS: FOSF produces high rates of PSA-determined and symptomatic response in 'hormone-refractory' prostate cancer. Toxicity and ease of administration compare favorably with those reported for CHT regimens used in this setting. The role of estrogens in prostate cancer should be redefined.
BACKGROUND: Although not clearly defined, 'hormone refractory' prostate cancer implies disease progression after orchiectomy +/- antiandrogens. Patients in this setting are usually offered chemotherapy protocols which often lead to significant toxicity and expense. In search of a well-tolerated, active, 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 indicated by 2 consecutively rising PSA determinations) after > or = 2 hormonal treatments (including surgical or chemical orchiectomy and a median of 3 prior treatment lines) received fosfestrol 100 mg t.i.d. per 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 > or = 50 decrease of PSA levels for longer than one month. 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 present in 73% of patients. RESULTS:CR + PR were observed in 79% (95% confidence interval: 66%-92%). The median time to progression was seven months. Pain remained stable or improved in 34% and 53%, respectively, of symptomatic patients with PSA response. Toxicity included worsening of gynecomastia, peripheral edema, and deep vein thrombosis (8%). No treatment-related deaths occurred. Uni- and multivariate analyses failed to identify predictive factors for response. PSA response was associated with significantly longer survival (13 vs. 7 months, P < 0.05 by Mantel-Haentzel). CONCLUSIONS: FOSF produces high rates of PSA-determined and symptomatic response in 'hormone-refractory' prostate cancer. Toxicity and ease of administration compare favorably with those reported for CHT regimens used in this setting. The role of estrogens in prostate cancer should be redefined.
Authors: Joan Carles; Daniel Castellano; Miguel Ángel Climent; Pablo Maroto; Rafael Medina; Antonio Alcaraz Journal: Clin Transl Oncol Date: 2012-03 Impact factor: 3.405