title: Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.
abstract: OBJECTIVE
  This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with good-risk nonseminomatous germ cell tumors.
  
  
  METHODS
  Between September 1989 and May 1993, a total of 598 patients with good-risk nonseminomatous germ cell tumors were randomized to receive four cycles of either BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3, and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20 mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the carboplatin dose was calculated from the glomerular filtration rate to achieve a serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21-day intervals to a total of four cycles.
  
  
  RESULTS
  Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P = .009). There were 30 treatment failures in the 300 patients allocated to BEP and 79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P < .001), which led to failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%) and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P = .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90% (95% CI, 86% to 94%), respectively.
  
  
  CONCLUSIONS
  With these drug doses and schedules, combination chemotherapy based on carboplatin was inferior to that based on cisplatin. This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.
authors.affiliation: Medical Research Council Testicular Tumour Working Party, London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Horwich
authors.forename: D T
authors.initials: DT
authors.lastname: Sleijfer
authors.forename: S D
authors.initials: SD
authors.lastname: Fosså
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
authors.forename: R T
authors.initials: RT
authors.lastname: Oliver
authors.forename: M H
authors.initials: MH
authors.lastname: Cullen
authors.forename: G M
authors.initials: GM
authors.lastname: Mead
authors.forename: R
authors.initials: R
authors.lastname: de Wit
authors.forename: P H
authors.initials: PH
authors.lastname: de Mulder
authors.forename: D P
authors.initials: DP
authors.lastname: Dearnaley
authors.forename: P A
authors.initials: PA
authors.lastname: Cook
authors.forename: R J
authors.initials: RJ
authors.lastname: Sylvester
authors.forename: S P
authors.initials: SP
authors.lastname: Stenning
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D018237:Germinoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D011379:Prognosis; D012074:Remission Induction; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D001761:Bleomycin; D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin