title: Amifostine does not prevent platinum-induced hearing loss associated with the treatment of children with hepatoblastoma: a report of the Intergroup Hepatoblastoma Study P9645 as a part of the Children's Oncology Group.
abstract: BACKGROUND
  The current study was conducted to determine whether amifostine is effective in reducing the toxicities associated with the administration of platinum-containing regimens in children with hepatoblastoma (HB).
  
  
  METHODS
  Patients were enrolled on P9645 beginning in March of 1999. Patients who had stage I/II disease received treatment with 4 cycles of combined cisplatin, 5-fluorouracil, and vincristine (C5V) with or without amifostine. Patients who had stage III/IV disease were randomized to receive treatment with 6 cycles of either C5V with or without amifostine or carboplatin alternating with cisplatin (CC) with or without amifostine. Patients who were randomized to receive amifostine were given a dose of 740 mg/m2 intravenously over 15 minutes before each administration of a platinum agent.
  
  
  RESULTS
  Eighty-two patients were considered in a special interim analysis of the incidence of toxicity. The disease outcome for patients who received amifostine was similar to the outcome for patients who did not receive amifostine (P=.22). The incidence of significant hearing loss (>40 dB) was similar for patients who did or did not receive amifostine (38% [14 of 37 patients] vs 38% [17 of 45 patients], respectively; P=.68). There were no differences in the incidence of renal or bone marrow toxicities evaluated. Patients who received amifostine had a higher incidence of hypocalcemia (5% vs 0.5%; P=.00006).
  
  
  CONCLUSIONS
  Amifostine in the doses and schedule used in this study failed to significantly reduce the incidence of platinum-induced toxicities in patients with HB.
authors.affiliation: Department of Pediatrics, Aflac Cancer Center of Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA. howard.katzenstein@choa.org
authors.forename: Howard M
authors.initials: HM
authors.lastname: Katzenstein
authors.forename: Kay W
authors.initials: KW
authors.lastname: Chang
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Milton J
authors.initials: MJ
authors.lastname: Finegold
authors.forename: Jon
authors.initials: J
authors.lastname: Rowland
authors.forename: Marleta
authors.initials: M
authors.lastname: Reynolds
authors.forename: Alberto
authors.initials: A
authors.lastname: Pappo
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Marcio
authors.initials: M
authors.lastname: Malogolowkin
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D016190:Carboplatin / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced* / Q000517:prevention & control*; D018197:Hepatoblastoma / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011837:Radiation-Protective Agents / Q000494:pharmacology*
chemical_list: D011837:Radiation-Protective Agents; D016190:Carboplatin; D004999:Amifostine; D002945:Cisplatin