title: Finasteride and flutamide as potency-sparing androgen-ablative therapy for advanced adenocarcinoma of the prostate.
abstract: OBJECTIVE
  Androgen ablation with luteinizing hormone-releasing hormone (LHRH) agonists, orchiectomy, or oral estrogens has significant untoward sexual side effects. We evaluated a combination of finasteride and flutamide as potency-sparing androgen ablative therapy (AAT) for advanced adenocarcinoma of the prostate. In addition, we evaluated whether finasteride provided additional intraprostatic androgen blockade to flutamide.
  
  
  METHODS
  Twenty men with advanced prostate cancer were given flutamide, 250 mg orally three times daily. Serum prostate-specific antigen (PSA) values were measured weekly. At a nadir PSA value, finasteride, 5 mg orally every day, was added. PSA values were then measured weekly until a second nadir PSA value was achieved. Sexual function was evaluated at baseline, at the second nadir PSA value, and every 3 months thereafter. Testosterone, dihydrotestosterone (DHT), and dehydroepiandrostenedione (DHEA) levels were measured at baseline and at the first and second nadir PSA values.
  
  
  RESULTS
  The median follow-up period was 16.9 months. Therapy failed in 1 patient with Stage D2 disease at 12 months, but an additional response to subsequent LHRH agonist therapy was observed. One patient developed National Cancer Institute grade 3 diarrhea and was withdrawn from the study. Seven of 20 men developed mild gynecomastia, and 3 of 20 developed mild transient liver function test elevations. Mean PSA levels were 94.6 +/- 38.2 ng/mL at baseline and 7.8 +/- 2.7 and 4.7 +/- 2.2 ng/mL at the first and second PSA nadir values, respectively (P = 0.034). Mean percent decline in PSA value from baseline was 87.0 +/- 3.1% with flutamide alone and 94.0 +/- 1.9% with both flutamide and finasteride (P = 0.001). Eleven of 20 men were potent at baseline. At the second nadir PSA value, 9 (82%) of 11 were potent, whereas 2 (18%) of 11 were impotent. With longer follow-up (median 16.4 months), 6 (55%) of 11 men were potent, 2 (18%) of 11 were partially potent, and 3 (27%) of 11 were impotent. With flutamide alone, testosterone rose a mean of 77 +/- 14.7% of baseline (P = 0.0001), DHEA fell a mean of 32.4 +/- 4.6% (P = 0.0001), and DHT was unchanged. With the addition of finasteride, testosterone rose another 14 +/- 6% (P = 0.06, not significant), DHEA was unchanged, and DHT fell a mean of 34.8 +/- 4.7% (P = 0.0009).
  
  
  CONCLUSIONS
  Finasteride and flutamide were safe and well tolerated as AAT for advanced prostate cancer. Finasteride provided additional intraprostatic androgen blockade to flutamide, as measured by additional PSA suppression. Sexual potency was preserved initially in most patients, although there was a reduction in potency and libido in some patients on longer follow-up. Further evaluation of this therapy is needed.
authors.affiliation: Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: A
authors.initials: A
authors.lastname: Brufsky
authors.forename: P
authors.initials: P
authors.lastname: Fontaine-Rothe
authors.forename: K
authors.initials: K
authors.lastname: Berlane
authors.forename: P
authors.initials: P
authors.lastname: Rieker
authors.forename: M
authors.initials: M
authors.lastname: Jiroutek
authors.forename: I
authors.initials: I
authors.lastname: Kaplan
authors.forename: D
authors.initials: D
authors.lastname: Kaufman
authors.forename: P
authors.initials: P
authors.lastname: Kantoff
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007172:Erectile Dysfunction / Q000517:prevention & control*; D018120:Finasteride / Q000627:therapeutic use*; D005485:Flutamide / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D019529:Sexuality / Q000187:drug effects; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D004791:Enzyme Inhibitors; D018120:Finasteride; D005485:Flutamide; D017430:Prostate-Specific Antigen