title: A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group.
abstract: OBJECTIVE
  To compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing 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. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days).
  
  
  RESULTS
  With a median duration of follow-up of 49 weeks, time to treatment failure, the primary endpoint, was significantly (P = 0.005) better for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group. Patients in the flutamide plus LHRH-A group were 34% more likely to fail treatment over the given time period, as indicated by the hazard ratio of 0.749 (95% confidence interval, 0.61 to 0.92) for bicalutamide plus LHRH-A to flutamide plus LHRH-A. Results for secondary endpoints (survival, quality of life, and subjective response) were similar between groups. 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 well tolerated and provides superior efficacy to flutamide plus LHRH-A with respect to time to treatment failure. Assessment of the effects of these regimens on longer term survival requires additional time for follow-up.
authors.affiliation: Eastern Virginia Medical School, Norfolk, 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: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016001:Confidence Intervals; D004311:Double-Blind Method; D005485:Flutamide / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D017273:Goserelin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012044:Regression Analysis; D015996:Survival Rate; D014105:Tosyl Compounds; D017211:Treatment Failure
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; D005485:Flutamide; C053541:bicalutamide; D017430:Prostate-Specific Antigen; D016729:Leuprolide