Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hearing loss from chemotherapy underestimated

12.12.2005


OHSU study shows platinum-based ototoxicity in children prevalent, but new drugs offer prevention hope



By 14, Peter Johnson had survived brain cancer and a relapse of the disease in his shoulder. But it was treatment for the last tumor that would create his life’s greatest challenges.

Johnson, now 33, has suffered since 1986 from the effects of ototoxicity, a condition in which platinum-based chemotherapy drugs, such as carboplatin and the more common cisplatin, damage the tiny hair cells in the inner ear that vibrate in response to sound waves. This leads to progressive, irreversible hearing loss and reduced quality of life for patients.


Despite surgery and intense radiation therapy to remove the brain tumor, Johnson says the hearing loss resulting from the chemotherapy for the shoulder tumor has been the most disabling.

"The hearing loss is difficult," said Johnson, a Portland resident who started losing his hearing in 1986, about a year after his chemotherapy treatment for the shoulder tumor ended. "What I don’t think the general public understands is that surviving cancer isn’t the same as a broken leg. Once the leg is healed, you’re pretty much back to normal. Once you survive cancer, the after-effects are numerous and you just keep discovering them."

To scientists at Oregon Health & Science University, Johnson’s experience is not surprising. A new study published in the current edition of the Journal of Clinical Oncology found that ototoxicity’s frequency and severity, as well as its long-term effects on development, have long been underreported by the medical community.

The research found that a well-known classification system doctors use for reporting toxicities in patients, the National Cancer Institute’s Common Terminology Criteria for Adverse Events, or CTCAE, doesn’t consider high-frequency hearing loss, allowing the magnitude of ototoxicity in children treated with platinum agents to be miscalculated.

The purpose of the study is "to make people aware that this is more common than people think and we need to follow this issue," said Kristy Gilmer Knight, M.S., a pediatric audiologist at OHSU’s Doernbecher Children’s Hospital and the study’s lead author.

Knight said a major problem for doctors trying to diagnose hearing loss from ototoxicity is that it’s not that obvious. "The way it manifests itself is not that children lose all their hearing," she said. "The way it manifests itself is tricky. The typical presentation is high-frequency hearing loss, and so it may not look like they’re having a problem, especially when communicating one-on-one in a quiet room. And kids won’t complain about not understanding what was said when they’re really little."

And that can lead to development issues for children. A 1998 study that evaluated the educational performance and social-emotional functioning of about 1,200 children with minimal hearing loss found that 37 percent failed at least one grade in school compared with the normal rate of 3 percent. They also had more problems with behavior, energy, stress, self-esteem and social support.

OHSU researchers tested the hearing of 67 patients, ages 8 months to 23 years, who received platinum-based chemotherapy. Data was analyzed to determine the length of time to hearing loss using criteria from the American Speech-Language-Hearing Association, or ASHA, and the effects of treatment and patient characteristics on the incidence and severity of ototoxicity.

According to the study, hearing loss was found in 61 percent of patients, with average onset beginning 135 days after chemotherapy. This included 55 percent of children treated with cisplatin; 38 percent of children treated with cisplatin’s less-toxic derivative, carboplatin; and 84 percent of children treated with both agents. Children treated for osteosarcoma, neuroblastoma and medulloblastoma, the form of brain cancer Johnson had, experienced greater incidence and severity of hearing loss.

But researchers say many of these children are falling through the cracks. The study found that while the ASHA criteria and CTCAE grading scale were similar in how they defined hearing loss progression, results from clinical trials often focus only on CTCAE grade 3 toxicity, which represents hearing loss requiring therapeutic intervention, and grade 4, which requires a cochlear implant and additional speech and language development services. The study said agreement between the CTCAE and ASHA criteria was "inadequate."

"By tradition, many published clinical trials report only grade 3 and 4 CTCAE toxicities," the study explained. "In the case of hearing loss, this would leave grades 1 and 2 ototoxicity unreported, thereby underestimating the magnitude of ototoxicity in children treated with platinum agents. We believe that CTCAE grade 1 and 2 hearing losses are significant in children and should therefore be considered and reported." The study found that 36 percent of patients who were examined would not have been reported as having ototoxicity if only CTCAE grades 3 and 4 were considered.

Scientists want to boost awareness of ototoxicity because it may soon be preventable. Nancy Doolittle, Ph.D., associate professor of neurology, OHSU School of Medicine, and a researcher in the Blood Brain Barrier Program, which studies methods for breaching the brain’s natural defense system to deliver chemotherapy compounds to tumors, has shown that sodium thiosulfate (STS) decreased hearing loss in patients with malignant brain tumors who were treated with carboplatin chemotherapy, which is given with the blood-brain barrier disruption technique. When STS was given four hours after carboplatin, ototoxicity decreased from 84 percent of patients to 29 percent.

The OHSU study team is developing protocols for a clinical trial of a second potential chemo-protectant called N-acetylcysteine, or NAC. The drug, typically used to treat people with Tylenol poisoning, prevented platinum-induced ototoxicity in rats in a study published in mid-2004. NAC may prevent hearing loss by binding to cisplatin’s platinum molecules, inactivating them. And as a free radical scavenger, it hunts down highly reactive atom clusters believed to cause similar hearing loss caused by noise trauma.

The main aim is to determine a safely tolerated dose of NAC in humans. Once the safe dose is determined, Phase 2 efficacy testing begins to see if NAC, combined with STS, will protect hearing.

"One of the strategies for improving survival is increasing doses of chemotherapy," Doolittle said. "Because larger doses may cause more toxicity, we have to be able to address the toxicity. Maintaining quality of life by maintaining hearing is really important."

While the damage has been done to his own hearing, Johnson hopes drugs, such as STS and NAC, can help prevent the hearing loss in other cancer survivors. He also hopes to use his law degree and his experience as a law librarian and paralegal to advocate for others who’ve experienced hearing loss, which required Johnson to learn lip reading, relish television shows and movies with closed captioning, dread telephone calls and, ultimately, get a cochlear implant for his right ear.

"The fact of the matter is I could put out the same quality of work everybody else could, but I needed a half hour longer," said Johnson, who developed dyslexia as a result of the radiation treatment and chemotherapy. In his professional experiences, Johnson notes that "the real world doesn’t want to give you an extra half hour to do what needs to be done, though."

Jonathan Modie | EurekAlert!
Further information:
http://www.ohsu.edu

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>