title: Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study--Pediatric Oncology Group 9049 and Children's Cancer Group 8882.
abstract: OBJECTIVE
  To determine in a randomized comparison whether combination chemotherapy with high-dose cisplatin (HDPEB) improves the event-free (EFS) and overall (OS) survival of children and adolescents with high-risk malignant germ cell tumors (MGCT) as compared with standard-dose cisplatin (PEB) and to compare the regimens' toxicity.
  
  
  METHODS
  Between March 1990 and February 1996, 299 eligible patients with stage III and IV gonadal and extragonadal (all stages) MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. Chemotherapy included bleomycin 15 units/m(2) on day 1, etoposide 100 mg/m(2) on days 1 through 5, and either high-dose cisplatin 40 mg/m(2) on days 1 through 5 (HDPEB; n = 149) or standard-dose cisplatin 20 mg/m(2) on days 1 through 5 (PEB; n = 150). Patients were evaluated after four cycles of therapy, and those with residual disease underwent surgery. Those with malignant disease in resected specimen received two additional cycles of their assigned regimen.
  
  
  RESULTS
  One hundred thirty-four eligible patients with advanced testicular (n = 60) or ovarian (n = 74) tumors and 165 with stage I to IV extragonadal tumors were enrolled. HDPEB treatment resulted in significantly improved 6-year EFS rate +/- SE (89.6% +/- 3.6% v 80.5% +/- 4.8% for PEB; P =.0284). There was no significant difference in OS (HDPEB 91.7% +/- 3.3% v PEB 86.0% +/- 4.1%). Tumor-related deaths were more common after PEB (14 deaths v two deaths). Toxic deaths were more common with HDPEB (six deaths v one death). Other treatment-related toxicities were more common with HDPEB.
  
  
  CONCLUSIONS
  Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT. The OS is similar in both regimens, and the significant toxicity associated with HDPEB limits its use.
authors.affiliation: Wayne State University School of Medicine and Children's Hospital of Michigan, Detroit, MI, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cushing
authors.forename: Roger
authors.initials: R
authors.lastname: Giller
authors.forename: John W
authors.initials: JW
authors.lastname: Cullen
authors.forename: Neyssa M
authors.initials: NM
authors.lastname: Marina
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lauer
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Olson
authors.forename: Paul C
authors.initials: PC
authors.lastname: Rogers
authors.forename: Paul
authors.initials: P
authors.lastname: Colombani
authors.forename: Frederick
authors.initials: F
authors.lastname: Rescorla
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Billmire
authors.forename: Charles D
authors.initials: CD
authors.lastname: Vinocur
authors.forename: Edith P
authors.initials: EP
authors.lastname: Hawkins
authors.forename: Mary Margaret
authors.initials: MM
authors.lastname: Davis
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Perlman
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Robert P
authors.initials: RP
authors.lastname: Castleberry
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005047:Etoposide; D005260:Female; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin