Evaluation of amifostine for protection against cisplatin-induced serious hearing loss in children treated for average-risk or high-risk medulloblastoma

Neuro Oncol. 2014 Jun;16(6):848-55. doi: 10.1093/neuonc/not241. Epub 2014 Jan 10.

Abstract

Background: The purpose of this study was to evaluate amifostine for protection from cisplatin-induced serious hearing loss in patients with average-risk medulloblastoma by extending a previous analysis to a much larger sample size. In addition, this study aimed to assess amifostine with serious hearing loss in patients with high-risk medulloblastoma treated with cisplatin.

Methods: Newly diagnosed medulloblastoma patients (n = 379; ages 3-21 years), enrolled on one of 2 sequential St. Jude clinical protocols that included 4 courses of 75 mg/m(2) cisplatin, were compared for hearing loss by whether or not they received 600 mg/m(2) of amifostine immediately before and 3 hours into each cisplatin infusion. Amifostine administration was not randomized. The last audiological evaluation between 5.5 and 24.5 months following protocol treatment initiation was graded using the Chang Ototoxicity Scale. A grade of ≥ 2b (loss requiring a hearing aid or deafness) was considered a serious event.

Results: Among average-risk patients (n = 263), amifostine was associated with protection from serious hearing loss (adjusted OR, 0.30; 95% CI, 0.14-0.64). For high-risk patients (n = 116), however, there was not sufficient evidence to conclude that amifostine prevented serious hearing loss (OR, 0.89; 95% CI, 0.31-2.54).

Conclusions: Although patients in this study were not randomly assigned to amifostine treatment, we found evidence in favor of amifostine administration for protection against cisplatin-induced serious hearing loss in average-risk but not in high-risk, medulloblastoma patients.

Keywords: audiology; brain neoplasms; late effects; ototoxicity; platinum drugs.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amifostine / therapeutic use*
  • Antineoplastic Agents / adverse effects*
  • Cerebellar Neoplasms / drug therapy*
  • Child
  • Child, Preschool
  • Cisplatin / adverse effects*
  • Female
  • Hearing Loss / chemically induced*
  • Hearing Loss / prevention & control
  • Humans
  • Male
  • Medulloblastoma / drug therapy*
  • Protective Agents / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Protective Agents
  • Amifostine
  • Cisplatin