Determinants of ototoxicity in 451 platinum-treated Dutch survivors of childhood cancer: A DCOG late-effects study

Eva Clemens, Andrica C. de Vries, Saskia F. Pluijm, Antoinette Am Zehnhoff-Dinnesen, Wim J. Tissing, Jacqueline J. Loonen, Eline van Dulmen-den Broeder, Dorine Bresters, Birgitta Versluys, Leontien C. Kremer, Heleen J. van der Pal, Martine van Grotel, Marry M. van den Heuvel-Eibrink

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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/m(2) 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
Original languageEnglish
Pages (from-to)77-85
JournalEuropean journal of cancer (Oxford, England
Publication statusPublished - Dec 2016


  • Carboplatin
  • Childhood cancer
  • Cisplatin
  • Furosemide
  • Munster classification
  • Ototoxicity

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