title: Low-dose continuous oral fosfestrol is highly active in 'hormone-refractory' prostate cancer.
abstract: 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.
  
  
  METHODS
  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.affiliation: Alexander Fleming Institute, Buenos Aires, Argentina. mauroorlando@hotmail.com
authors.forename: M
authors.initials: M
authors.lastname: Orlando
authors.forename: M
authors.initials: M
authors.lastname: Chacón
authors.forename: G
authors.initials: G
authors.lastname: Salum
authors.forename: D R
authors.initials: DR
authors.lastname: Chacón
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D016001:Confidence Intervals; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004054:Diethylstilbestrol; C004955:fosfestrol; D017430:Prostate-Specific Antigen