Cisplatin-induced hearing loss common among very young children early in treatment

September 07, 2021

3 minutes reading

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disclosures:
Meijer does not report any relevant financial disclosures. See the study for the relevant financial disclosures from all other authors. Brock does not report any relevant financial disclosures.

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Young children with cancer who received cisplatin chemotherapy had a higher incidence of cisplatin-induced hearing loss than older children, according to research results published in Cancer.

In addition, researchers found that hearing loss caused by cisplatin occurs early in therapy and is further affected by the total cumulative dose of the agent along with other ototoxic medications.

Data derived from Meijer AJM, et al. Cancer. 2021;doi:10.1002/cncr.33848.

“We have been researching ototoxicity in children with cancer for years within the [Canadian Pharmacogenomics Network for Drug Safety] consortium and at the Princess Máxima Center for Pediatric Oncology,” Annelot JM Meijer, MSc, researcher at the Princess Máxima Center for Pediatric Oncology in the Netherlands, Healio said. “Previous studies worldwide have focused on hearing loss related to cisplatin as a late effect in childhood cancer survivors. This type of hearing loss often develops early in treatment, but research on this direct effect remains limited.”

To gain a better understanding, Meijer and colleagues examined the course of hearing loss during treatment with cisplatin.

“Our understanding of clinical risk factors and their association with treatment-related hearing loss is still evolving and therefore it was of great importance to assess the influence of tumor type, carboplatin, cranial irradiation, vincristine and the overall duration of ototoxic co-medication on the course of development. of hearing loss over time,” she said.

Researchers retrospectively reviewed data on 368 Canadian children with cancer (52% male; 38%, age 5 years) who underwent a total of 2,052 audiological assessments (median, 5; range, 2-15) before, during, and after cisplatin treatment . Researchers assessed hearing loss according to the criteria of the International Society of Pediatric Oncology and used the Kaplan-Meier method to estimate the cumulative incidence of cisplatin-induced hearing loss for the total cohort, as well as by age.

Results showed an overall cumulative incidence of cisplatin-induced hearing loss of 59.7% (95% CI, 51.4-68.1) 3 years after initiation of treatment, with the highest incidence observed in children aged 5 years or younger vs older than 5 years (75% vs 48%, P < .001). Note that researchers saw a strong increase in the younger cohort at 3 months (27%; 95% CI, 21-35) and at 1 year (61%; 95% CI, 53-69).

According to a multivariate Cox regression model, factors influencing the development of cisplatin-induced hearing loss over time included the total cumulative dose of cisplatin at 3 months during therapy (per 100 mg/m2 increase: HR = 1.2; 95% CI, 1.01-1.41), vincristine treatment (HR = 2.87, 95% CI, 1.89-4.36) and total duration of co-administered antibiotics (>30 days: HR = 1.85 , 95% CI, 1.17-2.95).

“It is extremely important for oncologists to realize that optimal hearing and recognition of speech sounds are crucial for speech-language development in young children. [patients with cancer]’ said Meier. “If this is hampered by hearing loss, communication skills, school performance and social-emotional development are hampered.”

Therefore, audiological monitoring with every cisplatin cycle during childhood cancer therapy would be desirable, especially for young patients, she added.

Annelot JM Meijer

“Many contemporary clinical protocols require audiological assessments to take the second cycle of cisplatin, which could delay the early detection of hearing loss and application of interventions such as dose reduction of subsequent cisplatin administration,” Meijer told Healio. “Close audiological monitoring allows for timely counseling regarding the implications of the loss and compensatory strategies to reduce the adverse effect on communication and development.”

Researchers are now investigating the underlying mechanism that could explain the higher incidence of cisplatin-induced hearing loss in very young children.

“The central auditory pathway continues to develop from birth through the first few years of life, and these maturing structures may be more vulnerable to the toxic effect of cisplatin,” Meijer said. “In addition, it has been suggested that the long-term retention of cisplatin in the cochlea may be more pronounced in young pediatric patients. These hypotheses require more in-depth investigation.”

The study highlights the challenge platinum ototoxicity poses to oncologists and audiologists and the need to streamline care, according to an accompanying editorial from Penelope R. Brock, MD, PhD, MA, consultant pediatric oncologist at Great Ormand Street Hospital for Children NHS Foundation Trust in London.

“Teamwork is not a new phenomenon in oncology; we are already working with pathologists, radiologists, surgeons and other multidisciplinary team members,” Brock wrote. “However, to date, audiologists are not fully integrated into all cancer treatment teams. … If we want to make progress in this area, both clinical research into the scientific basis of the outcomes of modified treatments and a better multidisciplinary team working with the audiologists in real time will be necessary.”

References:

Brock PR. Cancer. 2021;doi:10.1002/cncr.33847.
Meijer AJM, et al. Cancer. 2021; doi: 10.1002/cncr.33848.

For more information:

Annelot JM Meijer, MSc, can be reached at Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands; e-mail: ajmmeijer-16@prinsesmaximacentrum.nl.

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