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Randomized Controlled Trial
. 2023 Mar;133(3):676-682.
doi: 10.1002/lary.30231. Epub 2022 May 27.

Ototoxicity of Long-Term α-Difluoromethylornithine for Skin Cancer Prevention

Cynthia L Chow  1 , Thomas Havighurst  2 , Taja Lozar  3 , Todd D Jones  4 , KyungMann Kim  2   3 , Howard H Bailey  3
Affiliations
Randomized Controlled Trial

Ototoxicity of Long-Term α-Difluoromethylornithine for Skin Cancer Prevention

Cynthia L Chow et al. Laryngoscope. 2023 Mar.

Abstract

Objective: Evaluate the effects of α-difluoromethylornithine (DFMO) on hearing thresholds as part of a randomized, double-blind, placebo-controlled trial.

Methods: Subjects were randomized and assigned to the control (placebo) or experimental (DFMO) group. DFMO or placebo were administered orally (500 mg/m2 /day) for up to 5 years.

Results: Subjects taking DFMO had, on average, increased hearing thresholds from baseline across the frequency range compared to subjects in the control group. Statistical analysis revealed this was significant in the lower frequency range.

Conclusions: This randomized controlled trial revealed the presence of increased hearing thresholds associated with long-term DFMO use. As a whole, DFMO may help prevent and treat certain types of cancers; however, it can result in some degree of hearing loss even when administered at low doses. This study further highlights the importance of closely monitoring hearing thresholds in subjects taking DFMO. Laryngoscope, 133:676-682, 2023.

Keywords: DFMO; cancer; chemoprevention; hearing loss.

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Conflict of interest statement

Conflict of Interest: The authors report no conflict of interest.

Figures

Figure 1.
Figure 1.
Study design and subject characteristics. Of the 334 subjects initially enrolled in the study, 291 subjects were randomized to the placebo or experimental group. Hearing loss data was available on 250 subjects. DFMO - α-difluoromethylornithine. BSA - body surface area.
Figure 2.
Figure 2.
Hearing Thresholds by Frequency at Baseline, 1 Year, End of Study and End of Study (last observation carried forward, LOCF). Hearing tresholds worsened over the course of this study in both the placebo and DFMO groups. DFMO - α-difluoromethylornithine. The error bars represent 95% confidence intervals.
See this image and copyright information in PMC

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