Cisplatin is a chemotherapy medication widely used to treat a
variety of cancers in both adults and children. Although effective,
cisplatin frequently causes permanent hearing loss and tinnitus (ringing
in the ears), resulting in functional disability for patients who
For young children in particular, hearing loss is especially
serious because it results in impaired language development, learning
and social interactions. Preventing ototoxicity, while preserving
chemotherapeutic efficacy, has been a long-standing goal of physicians,
scientists, parents and survivors.
‘There is a significant reduction in the incidence of hearing loss in children and adolescents with cancer who were treated with cisplatin and sodium thiosulfate compared to those who received cisplatin alone.’
Investigators from Children's Hospital Los Angeles and 37 other
Children's Oncology Group hospitals in the U.S. and Canada have
determined that sodium thiosulfate prevents cisplatin-induced hearing
loss in children and adolescents with cancer. Results of this
randomized, controlled, phase 3 study, called ACCL0431, have been
published in the early online edition of Lancet Oncology
"This federally-funded, cooperative group study is the first to show
that cisplatin-induced hearing loss can be reduced by about half in
children and adolescents being treated for cancer," said David R.
Freyer, director of the Survivorship & Supportive Care
Program in the Children's Center for Cancer and Blood Diseases at
Children's Hospital Los Angeles, who was lead author and chair of the
study. "It is an important step toward developing a safe and effective
strategy that will greatly improve quality of life for cancer
Historically, there have been no
proven treatments for preventing cisplatin-induced hearing loss tested
under the rigorous conditions of ACCL0431. Without otoprotection, the
only way to prevent hearing loss is to delete or decrease cisplatin
doses, which could render the cancer treatment less effective.
In ACCL0431, 125 eligible participants between the ages of one to 18
years with newly-diagnosed cancer were enrolled over a four year period.
The cancer diagnoses were hepatoblastoma, germ cell tumor,
medulloblastoma, neuroblastoma, osteosarcoma, or other cancer types
treated with cisplatin.
Study participants were randomized to receive
sodium thiosulfate or observation (control) during their chemotherapy.
Their hearing was assessed at baseline, following completion of the
chemotherapy regimen and one year later.
The investigators reported a significant reduction in the incidence
of hearing loss in participants who were treated with cisplatin and
sodium thiosulfate (29%) compared to those who received cisplatin alone
(56%). The greatest benefit was seen in children younger than five years
of age, who are most susceptible to, and also most affected by,
cisplatin-induced hearing loss.
Other effects of sodium thiosulfate were carefully monitored in the
study. Overall, sodium thiosulfate was tolerated well without any
serious adverse events. Survival from the cancer was not affected by
sodium thiosulfate among participants who had localized tumors.
survival appeared to be lower among those with metastatic disease who
received sodium thiosulfate. Additional research is needed to determine
what role sodium thiosulfate should have in preventing hearing loss in
specific subsets of patients being treated with cisplatin.