IU researcher awarded $5.7 million to study chemo-induced hearing loss, toxicities

INDIANAPOLIS–A researcher at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center has been awarded a five-year, $5.7 million National Cancer Institute grant to evaluate long-term health outcomes for cancer patients who receive platinum-based chemotherapies.

An internationally recognized expert on cancer survivorship, Lois B. Travis, MD, ScD, leads the ongoing study that could lessen cancer treatment side effects for millions of patients.

Nearly 6 million patients globally are diagnosed with a cancer each year in which first-line therapy potentially includes highly toxic, platinum-based chemotherapies. While the treatment may lead to hearing loss, ringing in the ears, numbness in hands and feet and other side effects, it is the only proven cure for the vast majority of testicular cancer patients.

When IU’s Lawrence Einhorn, MD, developed a revolutionary therapy for testicular cancer in the 1970s, he flipped the 95 percent mortality rate for the disease to a 95 percent survival rate. His regimen of platinum-based cisplatin and two other drugs continues to be the standard care for testicular cancer. Einhorn is the Livestrong Foundation Professor of Oncology at IU School of Medicine and a physician scientist at the IU Simon Comprehensive Cancer Center.

Now Travis, Einhorn and a team of researchers from other top cancer centers are following more than 2,000 testicular cancer survivors who are part of the largest clinical cohort of germ cell cancer survivors worldwide. The alliance of researchers leads The Platinum Study, which was established through a previous NCI grant awarded to Travis in 2012.

“We have shown with audiometric examination that 80 percent of the patients had hearing loss with one in five classified as severe to profound, levels at which hearing aids are recommended,” Travis, the Lawrence H. Einhorn Professor of Cancer Research at IU School of Medicine, said. Additionally, researchers found that 56 percent of patients had nerve damage called neuropathy and 40 percent had tinnitus or permanent ringing in their ears.

With this grant, researchers will tap into the existing cohort of patients who are part of the Platinum Study. The median age at diagnosis for testicular patients is 30, and the cohort’s median age now is 37. As patients age, researchers will continue to follow health changes, including if they are more susceptible to age-related hearing loss.

“We will examine the role of genetic variants in the platinum toxicities to try to identify high-risk subgroups,” Travis said.

The team of investigators wants to understand better which patients are at higher risk for these adverse outcomes and the daily effects of the toxicities.

“The goal is to follow this cohort for many decades to characterize the longitudinal trajectory of toxicities related to platinum-based chemotherapy,” she said. “For the first time, we will evaluate the impact and severity of the hearing loss and tinnitus on the patients’ physical, emotional and social functioning.”

Patients will complete questionnaires to track the different facets of their lives that are affected by hearing loss, or pain and numbness associated with neuropathy, as well as other toxicities. Researchers will also investigate the social and emotional consequences of the constant ringing in the ears, such as difficulty sleeping or concentrating.
Additionally, researchers will continue to analyze previously collected patient blood samples to track platinum levels, which can remain in the body for decades after chemotherapy is completed.

“Platinum is not completely excreted and is believed to be held in several body reservoirs. As tissue is remodeled with age, platinum regains access to the circulation,” Travis explained. “We will continue to measure the residual serum platinum levels.”

While cisplatin is used for many cancers, Travis notes that the testicular cancer patient cohort offers researchers a unique opportunity to study the toxicities.

“If we want to improve our understanding of long-term cisplatin-related toxicities, this is an ideal population,” she said. “When doing genetic studies, we know that all patients received about the same cumulative dose of cisplatin. We can then consider: who developed hearing loss and who didn’t, and what genetic and other factors are associated with this outcome?”

Ultimately, Travis hopes this research can determine which patients are most likely to experience adverse effects from cisplatin and then provide guidelines that could decrease damaging side effects, such as duration of treatments or improved symptom management.

“This is a critical part of my life’s mission: to decrease the cost of the cure for cancer survivors,” Travis said.

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Collaborators include researchers from Memorial Sloan Kettering Cancer Center (Darren Feldman, MD), Dana-Farber Cancer Institute (Neil Martin, MD), University of Pennsylvania (David Vaughn, MD), University of South Florida (Robert Frisina, PhD), Vanderbilt University (Nancy Cox, PhD), University of Chicago (Eileen Dolan, PhD), Princess Margaret Hospital (Robert Hamilton, MD), the Royal Marsden Hospital (Robert Huddart, PhD), University of Rochester (Chunkit Fung, MD), Loyola University (Heather Wheeler, PhD), Harvard School of Public Health (Howard Sesso, ScD), and the British Columbia Cancer Agency (Christian Kollmannsberger, MD).