Risk factors of ototoxicity after cisplatin-based chemo-irradiation in patients with locally advanced head-and-neck cancer: a multivariate analysis

Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1320-5. doi: 10.1016/j.ijrobp.2007.01.042. Epub 2007 Apr 6.

Abstract

Purpose: Cisplatin chemo-irradiation is increasingly used in locally advanced squamous cell carcinoma of the head and neck. The objective of this study is to determine risk factors of ototoxicity due to intra-arterial high-dose cisplatin chemoradiation.

Methods and materials: A prospective analysis of hearing thresholds at low and (ultra) high frequencies obtained before, during, and after treatment in 146 patients. Treatment consisted of intra-arterial infusion of high-dose cisplatin (150 mg/m(2), four courses) with sodium thiosulfate rescue and concurrent radiation therapy (70 Gy). Patient and chemoradiation variables were studied in a multivariate analysis.

Results: After treatment, 23% of the ears were under consideration for hearing aids because of therapy. Twenty-two percent of the patients developed an increase in air-bone gap >10 dB during or after therapy. In the multivariate explanatory analysis, cumulative dose of cisplatin and radiation therapy, and young age displayed a causal relationship with increased sensorineural hearing loss during and after therapy (p < 0.001). In the multivariate prediction analysis, pretreatment hearing level of the concerning ear was identified as an independent predictive factor for hearing capability after therapy (p < 0.0001).

Conclusions: Both cisplatin and radiation therapy were proven to induce sensorineural hearing loss, in this study with short-term follow-up. Of all patient and treatment variables studied, the patients pretreatment hearing level appeared to be the main predictive factor for hearing capability after high-dose intra-arterial cisplatin chemoradiation.

MeSH terms

  • Age Factors
  • Antidotes / therapeutic use
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / therapy*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Combined Modality Therapy / methods
  • Female
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / radiotherapy
  • Head and Neck Neoplasms / therapy*
  • Hearing / drug effects
  • Hearing / radiation effects
  • Hearing Loss, Sensorineural / chemically induced
  • Hearing Loss, Sensorineural / etiology*
  • Humans
  • Infusions, Intra-Arterial
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Radiation Dosage
  • Risk Factors
  • Thiosulfates / therapeutic use

Substances

  • Antidotes
  • Antineoplastic Agents
  • Thiosulfates
  • sodium thiosulfate
  • Cisplatin