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.
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.
Katzenstein
Howard M
HM
Department of Pediatrics, Aflac Cancer Center of Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA. howard.katzenstein@choa.org
Chang
Kay W
KW
Krailo
Mark
M
Chen
Zhengjia
Z
Finegold
Milton J
MJ
Rowland
Jon
J
Reynolds
Marleta
M
Pappo
Alberto
A
London
Wendy B
WB
Malogolowkin
Marcio
M
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*
D011837:Radiation-Protective Agents; D016190:Carboplatin; D004999:Amifostine; D002945:Cisplatin