title: Ototoxicity in a randomized phase III trial of intra-arterial compared with intravenous cisplatin chemoradiation in patients with locally advanced head and neck cancer.
abstract: OBJECTIVE
  Cisplatin concomitantly administered with radiotherapy is increasingly used in locally advanced head and neck squamous cell carcinoma. We aimed to compare the incidence of hearing loss between patients treated with intra-arterial high-dose cisplatin chemoradiation with sodium thiosulfate (CRT-IA) and intravenous high-dose cisplatin chemoradiation without sodium thiosulfate (CRT-IV).
  
  
  METHODS
  We conducted a prospective analysis of hearing thresholds at low and (ultra-) high frequencies obtained before, during, and after treatment in 158 patients. Patients were randomly assigned for either CRT-IA (150 mg/m(2), four courses) with sodium thiosulfate cisplatin neutralization or CRT-IV (100 mg/m(2), three courses) without rescue. All patients received concomitant radiation therapy (RT; 70 Gy).
  
  
  RESULTS
  CRT-IA resulted in approximately 10% less hearing loss at frequencies vital for speech perception, compared with CRT-IV (P < .001). In CRT-IA, fewer ears qualified for hearing aids (36% v 49%; P = .03). However, in both treatment arms, the incidence expressed in National Cancer Institute Common Terminology Criteria of Adverse Events (version 3) did not deviate (P > .14). Age, cumulative cisplatin dose, cumulative RT dose, and the considered frequency area determine the degree of hearing loss (P < .001). Cisplatin induced increasing hearing loss of 24% to 60% with increasing frequencies. RT induced hearing loss at speech frequencies of 9% to 12%.
  
  
  CONCLUSIONS
  Depending on the criteria used to assess hearing loss due to treatment, differences in ototoxicity between CRT-IA and CRT-IV were found in favor of CRT-IA. It is desirable to specify hearing loss criteria toward frequencies vital for speech perception, and to refine grading scales to reveal subtle and clinically relevant dissimilarities in ototoxicity between different treatment protocols.
authors: Department of Otorhinolaryngology, Academical Medical Centre, Amsterdam, the Netherlands. cl.zuur@vumc.nl
authors: Charlotte L
authors: CL
authors: Zuur
authors: Yvonne J
authors: YJ
authors: Simis
authors: Pauline E
authors: PE
authors: Lansdaal
authors: Augustinus A
authors: AA
authors: Hart
authors: Jan H
authors: JH
authors: Schornagel
authors: Wouter A
authors: WA
authors: Dreschler
authors: Coen R
authors: CR
authors: Rasch
authors: Alfons J
authors: AJ
authors: Balm
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001309:Auditory Threshold; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003131:Combined Modality Therapy; D007758:Ear, Inner / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy; D034381:Hearing Loss / Q000139:chemically induced*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D011879:Radiotherapy Dosage; D013885:Thiosulfates / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin