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

Cancer. 2009 Dec 15;115(24):5828-35. doi: 10.1002/cncr.24667.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amifostine / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carboplatin / adverse effects
  • Child
  • Child, Preschool
  • Cisplatin / adverse effects
  • Disease-Free Survival
  • Female
  • Hearing Loss / chemically induced*
  • Hearing Loss / prevention & control*
  • Hepatoblastoma / drug therapy*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Radiation-Protective Agents / pharmacology*

Substances

  • Radiation-Protective Agents
  • Carboplatin
  • Amifostine
  • Cisplatin