Deafness From Chemotherapy More Common Than We Think
Editor: We all know that some drugs and medications can cause hearing
loss, so it should be no surprise that those used in chemotherapy can do
so. Perhaps more surprising is the fact that the incidence of hearing
loss due to chemotherapy may be underreported.
Research at the Oregon Health & Science University addresses this
issue and offers potential treatment that may prevent hearing loss due
This article is reprinted with permission from Medicalnewstoday.com.
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
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
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
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
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
"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."
Other study co-authors included; Dale Kraemer, Ph.D., associate
professor, Department of Pharmacy Practice, Oregon State University; and
Edward Neuwelt, M.D., professor of neurology and neurological surgery,
OHSU School of Medicine and the Portland Veterans Affairs Medical
Center, and director of the OHSU Blood Brain Barrier Program. The study
was funded by the National Institute of Neurological Disorders and
Stroke, the National Institutes of Health and the U.S. Department of
Veterans Affairs. Dr. Neuwelt, OHSU, Portland Veterans Affairs Medical
Center and the Department of Veterans Affairs have a significant
financial interest in Adherex, a company that may have a commercial
interest in the results of this research and technology. This potential
conflict was reviewed and a management plan approved by the OHSU
Integrity Program Oversight Council and the Portland Veterans Affairs
Medical Center Conflict of Interest in Research Committee was