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Predictors of cisplatin-induced ototoxicity and survival in chemoradiation treated head and neck cancer patients.
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.
Afiliación
  • Teft WA; Department of Medicine, Western University, 1151 Richmond St., London, ON N6A3K7, Canada.
  • Winquist E; Department of Oncology, Division of Medical Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada; Department of Otolaryngology - Head and Neck Surgery, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON
  • Nichols AC; Department of Otolaryngology - Head and Neck Surgery, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada; Department of Oncology, Division of Surgical Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON
  • Kuruvilla S; Department of Oncology, Division of Medical Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada.
  • Richter S; Department of Oncology, Division of Medical Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada.
  • Parker C; Department of Otolaryngology - Head and Neck Surgery, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada.
  • Francis P; London Regional Cancer Program, London Health Sciences Centre, 800 Commissioners Rd. E., London, ON N6A5W9, Canada.
  • Trinnear M; Lawson Health Research Institute, 750 Baseline Rd. E., London, ON N6C2R5, Canada.
  • Lukovic J; Department of Oncology, Division of Radiation Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada.
  • Bukhari N; Department of Oncology, Division of Medical Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada.
  • Choi YH; Department of Epidemiology and Biostatistics, Kresge Building, UWO, London, ON N6A 5C1, Canada.
  • Welch S; Department of Oncology, Division of Medical Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada.
  • Palma DA; Department of Otolaryngology - Head and Neck Surgery, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada; Department of Oncology, Division of Radiation Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, O
  • Yoo J; Department of Otolaryngology - Head and Neck Surgery, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON N6A5W9, Canada; Department of Oncology, Division of Surgical Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E., London, ON
  • Kim RB; Department of Medicine, Western University, 1151 Richmond St., London, ON N6A3K7, Canada; Department of Physiology and Pharmacology, Medical Sciences Building, UWO, London, ON N6A 5C1, Canada; Department of Oncology, Division of Experimental Oncology, London Health Sciences Centre, Western Universit
Oral Oncol ; 89: 72-78, 2019 02.
Article en En | MEDLINE | ID: mdl-30732962
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Quimioradioterapia / Ototoxicidad / Neoplasias de Cabeza y Cuello Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Oral Oncol Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Quimioradioterapia / Ototoxicidad / Neoplasias de Cabeza y Cuello Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Oral Oncol Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido