title: Combined finasteride and flutamide therapy in men with advanced prostate cancer.
abstract: OBJECTIVE
  To evaluate the efficacy of combined finasteride and flutamide therapy in men with advanced prostate cancer by determining (1) the short-term tolerability of finasteride monotherapy and its effect on serum prostate-specific antigen (PSA) and hormone (testosterone, dihydrotestosterone) levels, and (2) the effects of the addition of flutamide on tolerability and on serum PSA and hormone levels.
  
  
  METHODS
  Thirteen hormone-naive men with advanced prostate cancer (4 with Stage D2, 1 with Stage D1, 1 with Stage D0, and 7 with rising PSA levels after radical prostatectomy [n = 2] or definitive radiation therapy [n = 5]) were initially treated with 5 mg finasteride daily. Flutamide (250 mg three times a day) was added after serum PSA levels stabilized.
  
  
  RESULTS
  Finasteride alone (median 5 weeks) had no significant effect on serum PSA levels (P > 0.05). Combined finasteride and flutamide resulted in a mean 91% reduction in serum PSA levels, with 85% of men achieving a nadir serum PSA level of less than 4.0 ng/mL and 46% achieving undetectable levels (0.2 ng/mL or less). Finasteride alone had no significant effect on serum testosterone levels (P > 0.05) but did result in a mean 74% reduction in serum dihydrotestosterone levels. Combined finasteride and flutamide resulted in a mean 56% increase in serum testosterone levels but had no additional effect on serum dihydrotestosterone levels (P > 0.05). Side effects occurred in 85% (gynecomastia or breast tenderness in 62% [8 of 13] and diarrhea in 23% [3 of 13]) of men on combined therapy. Potency was preserved in 66%. Combined finasteride and flutamide therapy was withdrawn from 15% (2 of 13) because of flutamide-induced diarrhea and from 23% (3 of 13) because of disease progression. All remaining patients (8 of 13) have serum PSA levels below 4.0 ng/mL and 4 of these 8 have undetectable levels. These men have received combined finasteride and flutamide for a median 11 months (range 6 to 19).
  
  
  CONCLUSIONS
  Finasteride monotherapy is inadequate therapy for advanced prostate cancer, but combined finasteride and flutamide may be a reasonable alternative for men with advanced prostate cancer who refuse conventional hormone therapy.
authors.affiliation: Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Ornstein
authors.forename: G S
authors.initials: GS
authors.lastname: Rao
authors.forename: B
authors.initials: B
authors.lastname: Johnson
authors.forename: E T
authors.initials: ET
authors.lastname: Charlton
authors.forename: G L
authors.initials: GL
authors.lastname: Andriole
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D018120:Finasteride / Q000008:administration & dosage; D005485:Flutamide / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D018120:Finasteride; D005485:Flutamide; D017430:Prostate-Specific Antigen