Featured Clinical Trial: Preventing Chemotherapy-related Hearing Loss in Young Cancer Patients
Posted Oct 04 2010 9:00pm
Preventing Chemotherapy-related Hearing Loss in Young Cancer Patients
Name of the Trial Phase III Randomized Study of Sodium Thiosulfate in Preventing Ototoxicity in Young Patients Receiving Cisplatin Chemotherapy for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy (COG-ACCL0431). See the protocol summary .
Dr. David Freyer
Principal Investigator Dr. David Freyer, Children’s Oncology Group
Why This Trial Is Important The chemotherapy drug cisplatin is a key part of treatment for many children and adolescents with cancer. However, treatment with cisplatin carries the risk of serious side effects , including irreversible hearing loss (ototoxicity). Although this drug can cause hearing loss in patients of all ages, children younger than age 5 are especially susceptible to cisplatin-induced ototoxicity. Hearing loss among young children is a particular concern because it interferes with their ability to learn language skills and acquire other knowledge and can result in lifelong disability and impaired quality of life .
Cisplatin-induced ototoxicity usually develops in both ears and typically progresses from losing the ability to hear high-frequency sound to losing the ability to hear low-frequency sound as the total cumulative dose increases. Some children develop high-frequency hearing loss with as little as one dose. As hearing loss progresses, the frequency range for understanding human speech is commonly affected.
Unfortunately, the cisplatin doses needed to treat many pediatric cancers often exceed the total dose at which hearing loss typically develops, and hearing loss is frequently the dose-limiting factor in their treatment. Without a way to protect hearing, patients, families, and physicians may be required to choose between optimal tumor treatment and preserving the ability to hear.
A drug called sodium thiosulfate may help prevent or lessen the degree of hearing loss in people undergoing cisplatin treatment. In animal studies, sodium thiosulfate protected hearing across several frequency ranges and did not interfere with the effectiveness of cisplatin or a similar drug, carboplatin, when given several hours after chemotherapy. A clinical trial in adults with brain tumors demonstrated that the drug could delay or prevent hearing loss in patients treated with high-dose intra-arterial carboplatin, and a pilot study in pediatric brain cancer patients showed that sodium thiosulfate was well tolerated by children undergoing similar carboplatin chemotherapy.
In this clinical trial, children and adolescents with cancer who are scheduled to receive cisplatin will be randomly assigned to receive sodium thiosulfate intravenously 6 hours after each cisplatin infusion or no additional treatment after each cisplatin infusion. All patients will have their hearing assessed at study entry, before each chemotherapy infusion, and at 4 weeks and 1 year after their last cisplatin treatment to determine whether sodium thiosulfate can prevent or reduce hearing loss in these patients. They will also try to determine whether sodium thiosulfate can prevent or reduce several other toxic effects of cisplatin, see if the drug affects event-free or overall survival , and examine the association of certain genetic mutations with the development of cisplatin-related hearing loss.
“We really feel that it’s important to achieve not only long-term survival for these patients but also a good quality of life, especially for young children, for whom hearing is so critically important,” said Dr. Freyer. “Our current standard of care with cisplatin is that we treat the child until the hearing loss is so severe that it requires a discussion between the physician and parents about stopping treatment. We’re hopeful that we may now have a means of preventing this very serious side effect.”
For More Information See the lists of entry criteria and trial contact information or call the NCI Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The call is toll free and confidential.