July 12, 2016
3 min read

Cumulative cisplatin dose linked to hearing loss among testicular cancer survivors

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Increasing cisplatin dose appeared significantly related to hearing loss among germ cell tumor survivors, according to study results.

“In addition to hearing loss, about 40% of patients also experienced tinnitus which was significantly correlated with reduced hearing,” Lois B. Travis, MD, ScD, Lawrence D. Einhorn professor of cancer research at Indiana University School of Medicine and director of the cancer survivorship research program at Indiana University Melvin and Bren Simon Cancer Center, said in a press release. “Our findings suggest that health care providers should, at a minimum, annually query patients who have received cisplatin-based chemotherapy about their hearing status, consulting with audiologists as indicated. Patients should also be urged to avoid noise exposure, drugs having adverse effects on hearing, and other factors that may further damage hearing.”

Lois Travis

Lois B. Travis

Cisplatin is widely used, but one of the most ototoxic drugs in clinical use. Due to the increasing number of cancer survivors in the United States, Travis and colleagues sought to evaluate the association between cumulative cisplatin dose and hearing ability among 488 men (median age at diagnosis, 31 years; range, 15-49) who had been treated with cisplatin-based therapy for a germ cell tumor.

Most patients in the cohort had received bleomycin, etoposide and cisplatin (60.5%) or etoposide and cisplatin (32%) chemotherapy regimens. The median cumulative cisplatin dose was 400 mg/m2 (range, 198-800).

Patients underwent audiological analyses that included audiograms (0.25 to 12 kHz), testing of middle ear function and tinnitus assessments. Median time from chemotherapy to audiometry was 4.25 years (range, 1-30.3).

Researchers used American Speech-Language-Hearing Association criteria to determine hearing loss severity. They categorized patients into quartiles based on hearing thresholds of age- and sex-matched controls.

Only 20% of patients had normal hearing; the other 80% had a hearing loss of at least 20 dB. Eighteen percent of patients had hearing loss ranging from severe to profound. Forty percent of patients had tinnitus, which appeared significantly correlated with reduced hearing at each frequency (P < .001).

Age-adjusted analyses showed increasing cisplatin dose was linked to worse hearing at thresholds ranging from 4 kHz (P = .021) to 10 kHz (P < .001). Further, cumulative cisplatin doses greater than 300 mg/m2 appeared to be associated with greater hearing loss severity (OR = 1.59; 95% CI, 1.14-2.21).

Every 100-mg/m2 increase in cisplatin dose was associated with a 3.2-dB impairment in age-adjusted overall hearing threshold (P < .001).

Compared with a normative population, patients who had received more than 300 mg/m2 cisplatin were more likely to be in a higher quartile of worse hearing than patients who received smaller doses (OR = 1.33; 95% CI, 0.95-1.85).

Ten percent of patients had noise-induced damage, but this appeared unaffected by cisplatin dose.

In an age- and cisplatin-adjusted analysis, hypertension — which was reported by 12.3% of patients — was significantly related to overall hearing threshold (4-12 kHz; P = .0066).

Researchers acknowledged they were unable to adjust for potentially differing distributions of hypertension, smoking and other potential confounders.

“We are the first to show definitively that in a significant number of the cancer survivors, they have hearing loss above-and-beyond age-related hearing loss,” Robert D. Frisina, PhD, professor in the department of chemical and biomedical engineering and director of the biomedical engineering program and global center for hearing and speech research at University of South Florida in Tampa, Florida, said in a press release. “They were different ages — 20s to 60s — so this was a new analysis.”

Cisplatin-induced ototoxicity might serve as a surrogate marker for susceptibility to platinum-induced healthy tissue damage, Jan Oldenburg, MD, PhD, of Akershus University Hospital and University of Oslo, and Jourik A. Gietema, MD, PhD, of University of Groningen in The Netherlands, wrote in an accompanying editorial.

“Because the validity of genetic studies is not better than their phenotype, ototoxicity as endpoint could facilitate identifying genetic causes of platinum toxicity,” they wrote. “Clinicians are reminded to think of and inform about ototoxicity before cisplatin treatment and to avoid additional ototoxic agents, such as aminoglycosides, in this patient population.” by Nick Andrews

Disclos ure: Travis reports no relevant financial disclosures. Frisina reports patents, royalties and other intellectual property for biomedical engineering patents related to hearing loss from University of South Florida, Tampa. Gietema reports research funding from AbbVie, Roche and Siemens. Please see the full study for a complete list of all other researchers' relevant financial disclosures.