Evaluating the Efficacy of Intratympanic Dexamethasone in Protecting Against Irreversible Hearing Loss in Patients on Cisplatin-Based Cancer Treatment: A Randomized Controlled Phase IIIB Clinical Trial

Abstract

Objective: To determine the efficacy of long-term high-dose intratympanic dexamethasone in protecting the hearing capacity of cancer patients undergoing cisplatin-based ototoxic treatment. Design: A randomized controlled phase IIIB clinical trial to evaluate the efficacy of dexamethasone in protecting against hearing loss in patients undergoing cisplatin treatment. The subjects participating in the clinical trial were patients with a neoplastic disease whose treatment protocol included cisplatin. The average dose of cisplatin was 444.87 mg (SD 235.2 mg). Treatment consisted of intratympanically administering dexamethasone via a passive diffusion device called Microwick (8 mg/24 h dose) from the start of treatment with cisplatin to 3 weeks after the last cycle. Patients were administered the medication to one ear, and the contralateral ear was used as the control. The treated ears were randomly chosen using a computer system (randomization). The hearing threshold was evaluated using pure tone audiometry before each cisplatin cycle. Results: Thirty-four patients were recruited over a 2-year period at a reference tertiary hospital, of whom 11 were excluded. Forty-six ears were analyzed (23 treated and 23 control ears). When treatment was completed, the audiometric analysis showed a higher hearing threshold in the study group than in the control group. Differences were statistically significant at frequencies of 500, 1000, and 6000 Hz: 4.9 dB (1.1 to 8.7), 5.5 dB (0.8 to 10.3), and 16 dB (3.2 to 28.7), respectively, (p < 0.05, 95% confidence interval), but were not clinically significant according to the ASHA hearing loss criteria. Both 8.69% infection complications during treatment and 34.8% permanent perforation at 6 mo were detected after device removal. Conclusions: Long-term high-dose intratympanic dexamethasone treatment did not prevent cisplatin-induced hearing loss.

Letter to the Editor: Comment on “Evaluating the Efficacy of Intratympanic Dexamethasone in Protecting Against Irreversible Hearing Loss in Patients on Cisplatin-Based Cancer Treatment: A Randomized Controlled Phase IIIB Clinical Trial” (Moreno and Belinchon 2022)

“…The negative results of Moreno and Belinchon study (Moreno and Belinchon 2022) contradicts our previous findings and encourages further research.…”

“…I have read with great interest the article by Moreno and Belinchon entitled “Evaluating the Efficacy of Intratympanic Dexamethasone in Protecting Against Irreversible Hearing Loss in Patients on Cisplatin-Based Cancer Treatment: A Randomized Controlled Phase IIIB Clinical Trial” (Moreno and Belinchon 2022). The authors examined the efficacy of continuous intra-tympanic delivery of Dexamethasone 8mg/24 hours via Microwick in the prevention of Cisplatin-induced hearing loss.…”

Curcumin-Encapsulated Chitosan-Coated Nanoformulation as an Improved Otoprotective Strategy for Ototoxic Hearing Loss

“…The auditory function was further evaluated, and hearing was restored by 30–45 dB SPL at varying frequencies following CUR-NP treatment. As mentioned earlier, Dex is an excellent candidate for ototoxic HL treatment clinically. − Regarding the obtained findings, CUR-CS/PLGA NPs protected OHCs from ototoxicity by CDDP at a dose of 4 μg/kg, but Dex did not exert a protective effect at this dose. Dex only exhibited the same level of the protective effect at a dose of 2000 μg/kg, indicating that the clinical application value of CUR was much better than Dex.…”

Prevention and treatment of platinum ototoxicity in adults: A systematic review

“…Moreno et al 2022). Safety outcomes for both trials reported slight pain and mild vertigo during the application, otological infections, and permanent tympanic perforation in 34.8% of the patients(Marshak et al, 2014, Moreno et al, 2022.…”

“…On the other hand, the N-acetylcysteine group did have a reduction in cisplatin hearing ototoxicity at 10,000 and 12,000 Hz (p<0.005) compared to placebo. Nonetheless, safety outcomes between study interventions were not reported (Yıldırım et al, 2010).Three investigations have evaluated the role of intratympanic corticosteroids to prevent CiO(Marshak et al, 2014, Moreno et al, 2022, Nasr et al, 2018. Two studies used dexamethasone and one methylprednisolone.…”