Ototoxic effects of supradose cisplatin with sodium thiosulfate neutralization in patients with head and neck cancer.

Abstract

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.

DESIGN:

Inception cohort study.

SETTING:

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

PATIENTS:

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

INTERVENTION:

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.

MAIN OUTCOME MEASURES:

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.

• Authors: R Madasu, M J Ruckenstein, F Leake, E Steere, K T Robbins
• Journal: Archives of otolaryngology--head & neck surgery (Arch Otolaryngol Head Neck Surg) Vol. 123 Issue 9 Pg. 978-81 (Sep 1997) ISSN: 0886-4470 [Print] United States
• PMID: 9305250 (Publication Type: Journal Article)

Chemical References

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

Topics

• Adult
• Antidotes (therapeutic use)
• Antineoplastic Agents (administration & dosage, adverse effects)
• Audiometry, Pure-Tone
• Auditory Threshold (drug effects)
• Carcinoma, Squamous Cell (drug therapy, radiotherapy)
• Chelating Agents (therapeutic use)
• Cisplatin (administration & dosage, adverse effects)
• Cochlea (drug effects)
• Cohort Studies
• Combined Modality Therapy
• Female
• Follow-Up Studies
• Head and Neck Neoplasms (drug therapy, radiotherapy)
• Hearing (drug effects)
• Hearing Disorders (physiopathology)
• Hearing Loss, High-Frequency (chemically induced)
• Humans
• Incidence
• Infusions, Intra-Arterial
• Male
• Middle Aged
• Radiotherapy Dosage
• Thiosulfates (therapeutic use)
• Tinnitus (chemically induced)
• Vestibular Diseases (chemically induced)