Ototoxic effects of supradose cisplatin with sodium thiosulfate neutralization in patients with head and neck cancer.
OBJECTIVE
To assess the incidence and magnitude of ototoxicity in patients undergoing an experimental targeted chemoradiation protocol incorporating extremely high-dose intra-arterial cisplatin therapy with systemic sodium thiosulfate neutralization for the treatment of advanced carcinomas of the head and neck.


METHODS
Inception cohort study.


METHODS
University-based, tertiary care referral center for advanced head and neck malignant disease.


METHODS
The first 70 patients with advanced carcinomas of the head and neck consecutively entered in the protocol.


METHODS
Patients received up to 4 weekly courses of intra-arterial cisplatin (150 mg/m2 per infusion), together with systemic sodium thiosulfate and external beam radiation (68-70 Gy). Audiometric analysis was performed before the initiation of therapy, and subsequent to the second and fourth cisplatin infusions.


METHODS
Audiometric thresholds. Ototoxicity was defined as an increase in pure-tone threshold of 15 dB at 1 frequency or 10 dB at 3 frequencies, between 250 and 4000 Hz.


RESULTS
The incidence of ototoxicity was 25% at 150 mg/m2, 50% at 300 mg/m2, 64% at 450 mg/m2, and 60% at 600 mg/m2. Hearing at frequencies of 2000 Hz or less was minimally or not affected. Previous hearing loss did not appear to affect the incidence of ototoxicity. A plateau of hearing loss at 60-dB hearing level, as noted by other authors, was not observed. There were no cases of debilitating tinnitus or of vestibular loss.


CONCLUSIONS
Ototoxicity did occur but was largely confirmed to the higher frequencies. Hearing losses resulting from this chemoradiation protocol were not sufficiently severe to alter its application.
Madasu
R
R
Department of Otolaryngology, Head and Neck Surgery, University of Tennessee, Memphis, USA.
Ruckenstein
M J
MJ
Leake
F
F
Steere
E
E
Robbins
K T
KT
D000328:Adult; D000931:Antidotes / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D002614:Chelating Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006309:Hearing / Q000187:drug effects; D006311:Hearing Disorders / Q000503:physiopathology; D006316:Hearing Loss, High-Frequency / Q000139:chemically induced; D006801:Humans; D015994:Incidence; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D013885:Thiosulfates / Q000627:therapeutic use*; D014012:Tinnitus / Q000139:chemically induced; D015837:Vestibular Diseases / Q000139:chemically induced
D000931:Antidotes; D000970:Antineoplastic Agents; D002614:Chelating Agents; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin