Ototoxicity in a randomized phase III trial of intra-arterial compared with intravenous cisplatin chemoradiation in patients with locally advanced head and neck cancer.
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.
Zuur
Charlotte L
CL
Department of Otorhinolaryngology, Academical Medical Centre, Amsterdam, the Netherlands. cl.zuur@vumc.nl
Simis
Yvonne J
YJ
Lansdaal
Pauline E
PE
Hart
Augustinus A
AA
Schornagel
Jan H
JH
Dreschler
Wouter A
WA
Rasch
Coen R
CR
Balm
Alfons J
AJ
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
D000970:Antineoplastic Agents; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin