title: Bicalutamide for advanced prostate cancer: the natural versus treated history of disease.
abstract: OBJECTIVE
  To determine the therapeutic effects of bicalutamide 200 mg in patients with prostate cancers of different hormone sensitivities.
  
  
  METHODS
  Patients with progressive prostate cancer were treated with bicalutamide 200 mg daily. Before treatment, patients' tumors were classified on the basis of prior hormone exposure and by serum testosterone levels into androgen-dependent and androgen-independent groups. Prior exposure to flutamide and response to flutamide withdrawal was also considered. Outcomes were reported independently on the basis of posttherapy changes in prostate-specific antigen (PSA), measurable disease, and radionuclide bone scans.
  
  
  RESULTS
  Outcomes varied by prior hormone exposure as a higher proportion of patients with progression of androgen-dependent tumors showed posttherapy PSA decreases of more than 50% or more than 80%, measurable disease regression, and improvement on radionuclide bone scans than did patients with androgen-independent progression. Within the category of androgen-independent progression, clinical benefit was observed in patients who had previously progressed on flutamide, independent of the response to flutamide withdrawal. Patients who had progressed on a gonadotropin-releasing hormone (GnRH) analog alone had a low response proportion, whereas those who progressed after two or more hormone therapies did not respond. Overall, the drug was well tolerated. After progression on bicalutamide monotherapy, one third of patients with androgen-dependent progression responded to medical castration with a GnRH analog.
  
  
  CONCLUSIONS
  Classifying patient tumors on the basis of prior hormone exposure permits a more precise estimate of the potential benefit of a specific hormone therapy for the individual patient. The precision is further increased by reporting the effects of a drug on each parameter of disease independently. The difference in outcomes for patients with androgen-independent progression suggests that the specific hormone therapy administered and the response to that therapy can influence the biology of the relapsing tumor and the sensitivity to subsequent therapies. The sensitivity to bicalutamide after progression on flutamide deserves further study.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. scherh@mskcc.org
authors.forename: H I
authors.initials: HI
authors.lastname: Scher
authors.forename: C
authors.initials: C
authors.lastname: Liebertz
authors.forename: W K
authors.initials: WK
authors.lastname: Kelly
authors.forename: M
authors.initials: M
authors.lastname: Mazumdar
authors.forename: C
authors.initials: C
authors.lastname: Brett
authors.forename: L
authors.initials: L
authors.lastname: Schwartz
authors.forename: G
authors.initials: G
authors.lastname: Kolvenbag
authors.forename: L
authors.initials: L
authors.lastname: Shapiro
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000728:Androgens; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary; D001842:Bone and Bones / Q000000981:diagnostic imaging; D018450:Disease Progression; D005485:Flutamide / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009570:Nitriles; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D011877:Radionuclide Imaging; D014105:Tosyl Compounds
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D005485:Flutamide; C053541:bicalutamide; D017430:Prostate-Specific Antigen