title: Maximal androgen blockade for patients with metastatic prostate cancer: outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy. Casodex Combination Study Group.
abstract: OBJECTIVE
  To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer.
  
  
  METHODS
  Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days).
  
  
  RESULTS
  At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting the definition for equivalence (< 1.25). With longer follow-up, overall mortality was 34%, with equivalent survival between groups: 32% of patients in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting the definition for equivalence (< 1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001).
  
  
  CONCLUSIONS
  In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.
authors.affiliation: Eastern Virginia Medical School, Norfolk 23507-1999, USA.
authors.forename: P
authors.initials: P
authors.lastname: Schellhammer
authors.forename: R
authors.initials: R
authors.lastname: Sharifi
authors.forename: N
authors.initials: N
authors.lastname: Block
authors.forename: M
authors.initials: M
authors.lastname: Soloway
authors.forename: P
authors.initials: P
authors.lastname: Venner
authors.forename: A L
authors.initials: AL
authors.lastname: Patterson
authors.forename: M
authors.initials: M
authors.lastname: Sarosdy
authors.forename: N
authors.initials: N
authors.lastname: Vogelzang
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: G
authors.initials: G
authors.lastname: Kolvenbag
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage; D000813:Anilides / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004311:Double-Blind Method; D005485:Flutamide / Q000008:administration & dosage; D005500:Follow-Up Studies; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009570:Nitriles; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014105:Tosyl Compounds
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; D005485:Flutamide; C053541:bicalutamide; D016729:Leuprolide