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

Authors

James G. Gurney, St. Jude Children's Research Hospital
Johnnie K. Bass, St. Jude Children's Research HospitalFollow
Arzu Onar-Thomas, St. Jude Children's Research Hospital
Jie Huang, St. Jude Children's Research Hospital
Murali Chintagumpala, Texas Children's Cancer Center and Hematology ServiceFollow
Eric Bouffet, Hospital for Sick Children University of Toronto
Tim Hassall, Hospital for Sick Children University of Toronto
Sridharan Gururangan, Royal Children's Hospital Brisbane
John A. Heath, Duke University Medical Center
Stewart Kellie, Royal Children's Hospital, Melbourne
Richard Cohn, The Children's Hospital at Westmead
Michael J. Fisher, Sydney Children's Hospital, RandwickFollow
Atmaram Pai Panandiker, St. Jude Children's Research Hospital
Thomas E. Merchant, St. Jude Children's Research Hospital
Ashok Srinivasan, St. Jude Children's Research Hospital
Cynthia Wetmore, St. Jude Children's Research Hospital
Ibrahim Qaddoumi, St. Jude Children's Research Hospital
Clinton F. Stewart, St. Jude Children's Research Hospital
Gregory T. Armstrong, St. Jude Children's Research HospitalFollow
Alberto Broniscer, St. Jude Children's Research HospitalFollow
Amar Gajjar, St. Jude Children's Research HospitalFollow

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/m2 cisplatin, were compared for hearing loss by whether or not they received 600 mg/m2 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. © 2014 The Author(s).

Publication Title

Neuro-Oncology

Recommended Citation

Gurney, J., Bass, J., Onar-Thomas, A., Huang, J., Chintagumpala, M., Bouffet, E., Hassall, T., Gururangan, S., Heath, J., Kellie, S., Cohn, R., Fisher, M., Panandiker, A., Merchant, T., Srinivasan, A., Wetmore, C., Qaddoumi, I., Stewart, C., Armstrong, G., Broniscer, A., & Gajjar, A. (2014). Evaluation of amifostine for protection against cisplatin-induced serious hearing loss in children treated for average-risk or high-risk medulloblastoma. Neuro-Oncology, 16 (6), 848-855. https://doi.org/10.1093/neuonc/not241