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.
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.
Cushing
Barbara
B
Wayne State University School of Medicine and Children's Hospital of Michigan, Detroit, MI, USA.
Giller
Roger
R
Cullen
John W
JW
Marina
Neyssa M
NM
Lauer
Stephen J
SJ
Olson
Thomas A
TA
Rogers
Paul C
PC
Colombani
Paul
P
Rescorla
Frederick
F
Billmire
Deborah F
DF
Vinocur
Charles D
CD
Hawkins
Edith P
EP
Davis
Mary Margaret
MM
Perlman
Elizabeth J
EJ
London
Wendy B
WB
Castleberry
Robert P
RP
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
D000970:Antineoplastic Agents; D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin