title: Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983.
abstract: OBJECTIVE
  To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC).
  
  
  METHODS
  Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m(2) in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual.
  
  
  RESULTS
  Accrual was from November 1998 to April 2009. A total of 169 patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different.
  
  
  CONCLUSIONS
  T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible patients demonstrated a 12% superior 3-year PFS with T-BEP, which was statistically significant.
authors.affiliation: Erasmus University Medical Center/Daniel den Hoed Cancer Center, Rotterdam, the Netherlands. r.dewit@erasmusmc.nl
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.forename: Iwona
authors.initials: I
authors.lastname: Skoneczna
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
authors.forename: Maria
authors.initials: M
authors.lastname: De Santis
authors.forename: August
authors.initials: A
authors.lastname: Garin
authors.forename: Nina
authors.initials: N
authors.lastname: Aass
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Witjes
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: White
authors.forename: José R
authors.initials: JR
authors.lastname: Germa-Lluch
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marreaud
authors.forename: Laurence
authors.initials: L
authors.lastname: Collette
mesh_terms: D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D017239:Paclitaxel; D002945:Cisplatin