Children’s Hospital Los Angeles Reports Technique to Significantly Reduce Chemotherapy-Induced Hearing Loss in Children

LOS ANGELES–(BUSINESS WIRE)–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, DO, MS
, 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
survivors.” Freyer is also professor of Clinical Pediatrics and Medicine
at the Keck School of Medicine of USC.

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 receive it.
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. 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 1 to 18 years
with newly-diagnosed cancer were enrolled over a 4 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 1 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 5 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. However,
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.

Additional contributors to the study include Lu Chen, Mark D. Krailo,
Doojduen Villaluna and Bonnie Bliss of the Keck School of Medicine of
USC; Kristin Knight, Edward A. Neuwelt of Oregon Health and Science
University; Brad H. Pollock of University of California Davis; Jagadeesh
Ramdas of Geisinger Medical Center, Danville, PA; Beverly Lange of
Children’s Hospital of Philadelphia; David Van Hoff and Michele L. Van
Soelen of Helen DeVos Children’s Hospital, Grand Rapids, MI; John
Wiernikowski of McMaster University, Hamilton, ON, Canada; and Lillian
Sung of the Hospital for Sick Children, Toronto, ON, Canada.

This research was supported by the Children’s Oncology Group and the
National Cancer Institute of the National Institutes of Health
(UG1-CA189955 and U10-CA095861).

About Children’s Hospital Los Angeles

Children’s Hospital Los Angeles has been named the best children’s
hospital in California and among the top 10 in the nation for clinical
excellence with its selection to the prestigious U.S. News & World
Report Honor Roll. Children’s Hospital is home to The Saban Research
Institute, one of the largest and most productive pediatric research
facilities in the United States. Children’s Hospital is also one of
America’s premier teaching hospitals through its affiliation since 1932
with the Keck School of Medicine of the University of Southern
California. For more information, visit
Follow us on Twitter,
and LinkedIn,
or visit our blog at


Children’s Hospital Los Angeles
Ellin Kavanagh