Determinants of ototoxicity in 451 platinum-treated Dutch survivors of childhood cancer: A DCOG late-effects study.
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/m2increase); 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.
Department of Pediatric Oncology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. Electronic address: e.clemens@erasmusmc.nl.
Eva
E
Clemens
Department of Pediatric Oncology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
Andrica C
AC
de Vries
Department of Pediatric Oncology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Saskia F
SF
Pluijm
Department of Phoniatrics and Pedaudiology, University of Münster, Münster, Germany.
Antoinette
A
Am Zehnhoff-Dinnesen
Department of Pediatric Oncology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Wim J
WJ
Tissing
Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
Jacqueline J
JJ
Loonen
Department of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands.
Eline
E
van Dulmen-den Broeder
Department of Pediatric Stem Cell Transplantation, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.
Dorine
D
Bresters
Department of Pediatric Oncology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
Birgitta
B
Versluys
Department of Pediatric Oncology, Academic Medical Center - Emma Children's Hospital, Amsterdam, The Netherlands.
Leontien C
LC
Kremer
Department of Pediatric Oncology, Academic Medical Center - Emma Children's Hospital, Amsterdam, The Netherlands.
Heleen J
HJ
van der Pal
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Martine
M
van Grotel
Department of Pediatric Oncology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Marry M
MM
van den Heuvel-Eibrink
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001301:Audiometry, Pure-Tone; D016190:Carboplatin / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004232:Diuretics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005665:Furosemide / Q000627:therapeutic use; D034381:Hearing Loss / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy*; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D012307:Risk Factors; D017741:Survivors; D055815:Young Adult
D000970:Antineoplastic Agents; D004232:Diuretics; D005665:Furosemide; D016190:Carboplatin; D002945:Cisplatin
Carboplatin; Childhood cancer; Cisplatin; Furosemide; Münster classification; Ototoxicity