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Predictors of cisplatin-induced ototoxicity and survival in chemoradiation treated head and neck cancer patients
Oral Oncology
  • Wendy A. Teft, Robarts Research Institute
  • Eric Winquist, University of Western Ontario
  • Anthony C Nichols, Western University
  • Sara Kuruvilla, Western University
  • Suzanne Richter, Western University
  • Christina Parker, Western University
  • Peggy Francis, London Health Sciences Centre
  • Maureen Trinnear, Lawson Health Research Institute
  • Jelena Lukovic, Western University
  • Nedal Buhkari, London Health Sciences Centre - Western University
  • Yun-Hee Choi, Western University
  • Steven Welch, London Health Sciences Centre-Western Univeristy
  • David Palma, Western University
  • John Yoo, London Health Sciences Centre-Western University
  • Richard B Kim, Western University
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Objectives: Cisplatin-induced ototoxicity is a common permanent consequence of curative chemoradiation for locally advanced head and neck squamous cell carcinoma (HNSCC). Predictors of ototoxicity in HNSCC were examined. Materials and methods: In this prospective, observational cohort study, 206 adult HNSCC patients underwent audiometric testing at baseline, during and after treatment with cisplatin-based chemoradiation. Ototoxicity was defined as >= grade 2 audiometric change from baseline (CTCAE v4.02). Relationships between clinical and pharmacogenetic (TPMT, COMT, ACYP2, CTR1, OCT2, MATE1, ABCC2, ABCC3, and ABCG2) covariates and ototoxicity, progression-free (PFS) and overall survival (OS) were assessed by Cox regression. Results: Weekly cisplatin resulted in lower ototoxicity risk while PFS and OS were similar compared to high dose cisplatin (P = 0.00035; HR = 0.18; 95% CI, 0.07-0.46). COMT (rs9332377) carriers had higher ototoxicity risk (P = 0.00556; HR = 1.72; 95% CI, 1.17-2.52) while MATE1 (rs2289669) A/A carriers were protected from ototoxicity (P = 0.01062; HR = 0.46; 95% CI, 0.26-0.84). Absence of the protective MATE1 allele among those who carry the risk allele in COMT predicted increased ototoxicity risk, (P = 0.00414; HR = 3.22; 95% CI, 1.45-7.17 and P = 0.00022; HR = 4.89; 95% CI, 2.11-11.36). Survival outcomes did not differ between carriers of protective or risk alleles. Conclusions: Weekly cisplatin dosing, COMT and MATE1 are predictors of ototoxicity without affecting treatment efficacy. COMT and MATE1 genotyping and weekly dosing may be a potential strategy for mitigating cisplatin-induced ototoxicity in HNSCC.

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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0
Citation Information
Wendy A. Teft, Eric Winquist, Anthony C Nichols, Sara Kuruvilla, et al.. "Predictors of cisplatin-induced ototoxicity and survival in chemoradiation treated head and neck cancer patients" Oral Oncology Vol. 89 (2019) p. 72 - 78
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