Highlights
- •A higher total cumulative dose cisplatin is associated with a higher risk of ototoxicity.
- •The risk of ototoxicity increased significantly up to a total cumulative dose cisplatin of 300 mg/m2.
- •Children with younger age at diagnosis have an increased risk of ototoxicity after platinum treatment.
- •Co-treatment with furosemide is independently associated with ototoxicity.
Abstract
Platinum-containing chemotherapeutics are efficacious for a variety of pediatric malignancies,
nevertheless these drugs can induce ototoxicity. However, ototoxicity data on large
cohorts of childhood cancer survivors (CCSs) who received platinum agents, but not
cranial irradiation are scarce. Therefore, we have studied the frequency and determinants
of ototoxicity in a cross-sectional multicenter CCS cohort, including the role of
co-medication since it has been suggested that these play a role in ototoxicity.
We have collected treatment data and audiograms from the medical records of CCS treated
in the seven pediatric oncology centres in The Netherlands. Ototoxicity was defined
as Münster grade ≥2b (>20 dB at ≥4–8 kHz).
Four-hundred-fifty-one CCS who received platinum agents, but not cranial irradiation
(median age at diagnosis: 4.9 years, range: 0.01–19 years) were included. The overall
frequency of ototoxicity was 42%. Ototoxicity was observed in 45% of the cisplatin-treated
CCS, in 17% of the carboplatin-treated CCS and in 75% of the CCS that had received
both agents. Multivariate analysis showed that younger age at diagnosis (odds ratio
[OR]: 0.6, 95% confidence interval [CI]: 0.5–0.6 per 5 years increase); higher total
cumulative dose cisplatin (OR: 1.2, 95% CI: 1.2–1.5 per 100 mg/m2 increase); and co-treatment with furosemide (OR: 2.3, 95% CI: 1.4–3.9) were associated
with ototoxicity.
We conclude that treatment with (higher total cumulative dose of) cisplatin, young
age and furosemide co-medication independently are associated with an increased risk
of ototoxicity in CCS. Future prospective studies are necessary to confirm the additive
risk of co-medication on the development of ototoxicity.
Keywords
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Article info
Publication history
Published online: November 04, 2016
Accepted:
September 20,
2016
Received in revised form:
September 15,
2016
Received:
June 10,
2016
Identification
Copyright
© 2016 Elsevier Ltd. All rights reserved.
