Ototoxicity in children treated for osteosarcoma.
BACKGROUND
Cisplatin is an effective agent against osteosarcoma. Ototoxicity from osteosarcoma treatment protocols has not been well defined. The aim of this study was to determine the incidence and risk factors for hearing loss in children treated for osteosarcoma.


METHODS
Eligible patients had osteosarcoma diagnosed and treated at the Dana-Farber Cancer Institute/Children's Hospital Boston from January 1, 1995 to December 12, 2004, were 3-18 years of age at diagnosis, and had a normal audiogram prior to the start of chemotherapy. Patients received cisplatin according to the standard practice or current open protocol. Patients who developed hearing loss during treatment had cisplatin held on an individualized basis. Hearing function was evaluated prior to the start of therapy, before each cycle, and off-therapy. Fisher's exact test and logistic regression models were used to identify univariate and independent predictors of hearing loss, respectively.


RESULTS
Seven out of nine patients (78%) who received cisplatin 120 mg/m(2)/day on 1 day developed hearing loss compared to 8/27 (30%) who received 60 mg/m(2)/day for 2 days (P = 0.019). Logistic regression showed that age, cumulative cisplatin dose, and administration of cisplatin 120 mg/m(2)/day were independent predictors of hearing loss. Cisplatin administered as 60 mg/m(2)/day for 2 days resulted in a low incidence (30%) of any hearing loss and a very low incidence (4%) of educationally significant hearing loss.


CONCLUSIONS
Cisplatin administered as 60 mg/m(2)/day for 2 days resulted in a low incidence of significant hearing loss. These results suggest that cisplatin as 120 mg/m(2)/day be avoided due to an unacceptable incidence of hearing loss.
Lewis
Matthew J
MJ
Department of Pediatric Hematology/Oncology, Dana Farber-Cancer Institute/Children's Hospital, Boston, Massachusetts 02115, USA.
DuBois
Steven G
SG
Fligor
Brian
B
Li
Xiaochun
X
Goorin
Allen
A
Grier
Holcombe E
HE
D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy* / Q000453:epidemiology
D000970:Antineoplastic Agents; D002945:Cisplatin