Portland, Ore.

Study Finds Delayed Use of Hearing Protectant Drugs Actually Decreases Hearing Loss

A new study may help provide greater protection against hearing loss in brain tumor patients treated with chemotherapy, while still allowing for effective use of cancer-fighting drugs. Researchers hope the work will help them save lives while maintaining a high quality of life for patients. Scientists in the Blood-Brain Barrier Program at Oregon Health Sciences University and the Portland Veterans Affairs Medical Center conducted this research. The National Institutes of Health and the Veterans Affairs Administration funded the work. The results are printed in the March issue of the journal Clinical Cancer Research.

The research centers on a commonly used and effective chemotherapy drug called carboplatin. The drug was first introduced in the 1980s. However, follow-up studies have shown that it can cause moderate to severe hearing loss in patients who received the drug in combination with temporary disruption of the blood-brain barrier. The blood-brain barrier is a naturally occurring central nervous system function that allows the brain to filter out dangerous chemicals. However, for patients with brain tumors, the barrier also can reduce the effectiveness of chemotherapy. By temporarily disrupting the blood-brain barrier, higher levels of chemotherapy drugs can reach tumors in the brain, allowing for more effective therapy. Technology to allow for opening of the blood-brain barrier was developed in the early 1980s by Neurosurgeon Edward Neuwelt, M.D., who now directs the university's Blood-Brain Barrier Program.

Past research by Neuwelt has shown that a protectant drug called sodium thiosulfate (STS) can be administered two hours following an infusion of carboplatin when the blood-brain barrier is re-established. In these cases, STS limits hearing loss. However, allowing at least two hours for the blood-brain barrier to re-establish is very important because STS given when the blood-brain barrier is open may cause toxicity. This study extended the infusion of STS to four hours after chemotherapy in an attempt to further reduce the chances of neurotoxicity.

"It was good news to learn that delayed administration of STS did not affect the drug's ability to protect against hearing loss," said Nancy Doolittle, Ph.D., R.N., lead author of the study and an assistant professor of neurology in OHSU's School of Medicine. "Unexpectedly, we also found that for those patients who received STS after four hours, hearing loss was even more diminished than those who received the hearing protectant after two hours. Following additional research, this discovery may be used to more effectively protect against hearing loss."

To conduct this research, scientists studied 60 patients between the ages of 4 and 67 who received chemotherapy assisted by blood-brain barrier disruption for malignant brain tumors. This included a comparison group of 19 patients who had received carboplatin chemotherapy before STS testing as a hearing protectant began in the late 1990s. More recently a total of 24 patients received STS two hours after chemotherapy. The remaining 17 patients received STS four hours after chemotherapy.

"These findings may have implications for patients receiving similar chemotherapy drugs, allowing the chemotherapy more time to work prior to administering the hearing protectant," said Neuwelt.

Researchers at OHSU are already conducting a separate study on a drug that is closely related to carboplatin called cisplatin. The drug is often used to treat various forms of cancer that often surface in children, but it is more toxic to hearing than carboplatin with up to 90 percent of children developing hearing loss. During this clinical trial physicians will administer STS eight hours after chemotherapy using cisplatin.

"We're interested in ensuring that the quality of life remains high for these kids. This research will also allow us to study the drug's effectiveness in a segment of our population with the best hearing of all and those who have the most to lose - our children," said Gary Jones, M.D., an associate professor of medicine in OHSU's School of Medicine and principal investigator of the study.

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