title: Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma.
abstract: OBJECTIVE
  The INT-0098 Intergroup Liver Tumor Study demonstrated no statistically significant differences in event-free and overall survival between patients randomized to treatment with either cisplatin + fluorouracil + vincristine (C5V) or cisplatin + doxorubicin. Results from this and other therapeutic trials suggested that cisplatin was the most active agent against hepatoblastoma. To increase the platinum dose-intensity, a novel regimen was developed alternating carboplatin and cisplatin (CC) every 2 weeks. The P9645 study was designed to compare the risk of treatment failure for patients with stage III/IV hepatoblastoma randomized to either C5V or CC.
  
  
  METHODS
  C5V was given according to INT-0098 and CC consisted of carboplatin at 700 mg/m2 on day 0 (560 mg/m2 after two cycles) followed by cisplatin 100 mg/m2 on day 14. Granulocyte colony-stimulating factor was used after each CC cycle. All patients received four to six cycles of chemotherapy.
  
  
  RESULTS
  From the time the study was opened until the time that random assignment was halted, 56 patients received CC and 53 patients received C5V. The 1-year event-free survival was 37% for patients receiving CC and 57% for those receiving C5V (P = .017). Patients randomly assigned to CC required more blood product support. As a result of a semiannual review by the Children's Oncology Group Data and Safety Monitoring Committee, random assignment was discontinued after 3 years of enrollment because the projected improvement in long-term outcome associated with CC was statistically excluded as a possible outcome of this trial.
  
  
  CONCLUSIONS
  Intensification of therapy by alternating platinum analogs increased the risk of adverse outcome in children with unresectable or metastatic hepatoblastoma.
authors.affiliation: Childrens Hospital Los Angeles, Division of Hematology-Oncology, Los Angeles, CA 90027, USA. mmalogolowkin@chla.usc.edu
authors.forename: Marcio H
authors.initials: MH
authors.lastname: Malogolowkin
authors.forename: Howard
authors.initials: H
authors.lastname: Katzenstein
authors.forename: Mark D
authors.initials: MD
authors.lastname: Krailo
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Laura
authors.initials: L
authors.lastname: Bowman
authors.forename: Marleta
authors.initials: M
authors.lastname: Reynolds
authors.forename: Milton
authors.initials: M
authors.lastname: Finegold
authors.forename: Brian
authors.initials: B
authors.lastname: Greffe
authors.forename: Jon
authors.initials: J
authors.lastname: Rowland
authors.forename: Kurt
authors.initials: K
authors.lastname: Newman
authors.forename: Richard B
authors.initials: RB
authors.lastname: Womer
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Robert P
authors.initials: RP
authors.lastname: Castleberry
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018197:Hepatoblastoma / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D016190:Carboplatin; D002945:Cisplatin; D005472:Fluorouracil