Predictors of cisplatin-induced ototoxicity and survival in chemoradiation treated head and neck cancer patients. (February 2019)

• Record Type: Journal Article
• Authors: Teft, Wendy A.; Winquist, Eric; Nichols, Anthony C.; Kuruvilla, Sara; Richter, Suzanne; Parker, Christina; Francis, Peggy; Trinnear, Maureen; Lukovic, Jelena; Bukhari, Nedal; Choi, Yun-Hee; Welch, Stephen; Palma, David A.; Yoo, John; Kim, Richard B.
• Is Part Of: Oral oncology. Volume 89(2019)
• Page Start: 72
• Page End: 78
• Publication Date: 2019-02
• Subjects: Cisplatin -- Ototoxicity -- Head and neck cancer -- MATE1 -- COMT; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2018.12.010
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: Weekly cisplatin dosing reduces cisplatin induced ototoxicity. MATE1 A/A subjects are at reduced ototoxicity risk. COMT carriers are at increased risk of cisplatin-induced ototoxicity. Treatment efficacy was not affected by weekly cisplatin dosing or MATE1/COMT status. Abstract: 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.