title: Efficacy of peripheral androgen blockade in prostate cancer patients with biochemical failure after definitive local therapy: results of Cancer and Leukemia Group B (CALGB) 9782.
abstract: BACKGROUND
  The treatment for prostate cancer patients with biochemical failure after local therapy remains controversial. Peripheral androgen blockade using a combination of a 5-alpha reductase inhibitor and an antiandrogen may allow control of the prostate-specific antigen (PSA). Because testosterone levels are not suppressed, this approach may be associated with less morbidity than conventional gonadal androgen suppression.
  
  
  METHODS
  All patients had undergone previous definitive local therapy and had evidence of a rising PSA >1ng/mL, with no evidence of recurrent disease. Patients received both finasteride, 5 mg orally per day, and flutamide, 250 mg orally 3× a day. Patients were followed for a PSA response and quality of life assessment.
  
  
  RESULTS
  Ninety-nine of 101 accrued patients were eligible. A ≥80% PSA decline was seen in 96 (96%) patients. The median time to PSA progression was 85 months. With a median follow-up of 10 years, the median survival time had not been reached, and the 5-year overall survival rate was 87%. Toxicity was mild, with 18 patients stopping for toxicity; 15 had diarrhea, 4 had gynecomastia, and 3 had transaminase elevation. Baseline Functional Assessment of Cancer Therapy Prostate Module and Treatment Outcome Index scores decreased by 5 points each at 6 months after enrollment.
  
  
  CONCLUSIONS
  The use of the finasteride/flutamide combination is feasible, and results in PSA declines of ≥80% in 96% of patients with serologic progression after definitive local therapy. There were no unexpected toxicities, and the change in quality of life was mild. Further evaluation of this or a similar regimen in a controlled clinical trial is warranted.
authors.affiliation: Division of Oncology, Department of Medicine, The Ohio State University School of Medicine, Columbus, Ohio, USA. Paul.monk@osumc.edu
authors.forename: J Paul
authors.initials: JP
authors.lastname: Monk
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
authors.forename: George
authors.initials: G
authors.lastname: Philips
authors.forename: Ellen
authors.initials: E
authors.lastname: Kaplan
authors.forename: Tim
authors.initials: T
authors.lastname: Ahles
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.forename: Nicholas
authors.initials: N
authors.lastname: Vogelzang
authors.forename: William K
authors.initials: WK
authors.lastname: Kelly
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018120:Finasteride / Q000008:administration & dosage; D005485:Flutamide / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D017211:Treatment Failure
chemical_list: D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D018120:Finasteride; D005485:Flutamide; D017430:Prostate-Specific Antigen