Intratympanic Dexamethasone Efficacy in Preventing Cisplatin-induced Tinnitus: A Randomized Controlled Phase IIIB Clinical Trial

OBJECTIVES: Cisplatin is a widely used chemotherapy agent. However, one of the side effects associated with cisplatin use is ototoxicity, causing hearing loss, tinnitus, and balance disorders. Furthermore, no preventive treatment for these conditions is currently available. Intratympanic administration of dexamethasone has reduced cisplatin-induced ototoxicity in vivo. However, clinical trials still need to be conducted to assess its efficacy in humans. The aim of this study was to assess the efficacy of intratympanic administration of dexamethasone in preventing tinnitus in patients with cancer undergoing cisplatin-based chemotherapy. DESIGN: We conducted a randomized, controlled, phase IIIB clinical trial. In this trial, we included patients with a neoplastic disease whose treatment protocol comprised cisplatin. During the 2-year study period, we recruited 34 patients at a reference tertiary hospital, of whom 11 were excluded. The treatment consisted of intratympanic administration of dexamethasone using a passive diffusion device called Microwick (8 mg/24 h dose). The dexamethasone administration started concurrently with cisplatin treatment and lasted three weeks after the last chemotherapy cycle. We used a computer system to randomly select one ear of each patient to administer the medication, whereas we used the contralateral ear as the control. In addition, we established another control group consisting of patients not treated with dexamethasone in either ear. Ten patients comprised the untreated control group. We evaluated the tinnitus using the Tinnitus Handicap Inventory at the disease onset and at the end of cisplatin treatment. RESULTS: The average dose of cisplatin was 444.87 mg (SD: 235.2 mg). We analyzed 46 ears of the experimental group (23 treated and 23 untreated) and 20 in the control group. After the treatment, no patient reported tinnitus in either ear. However, bilateral tinnitus was observed in 90% of patients who were not administered dexamethasone, with a mean worsening of 20.2 points on the Tinnitus Handicap Inventory. We observed 8.69% infection complications during dexamethasone treatment and 34.8% permanent perforation at 6 months after device removal. CONCLUSIONS: Intratympanic administration of a high dose of dexamethasone over an extended duration prevents cisplatin-induced tinnitus without affecting the hearing threshold.