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Effects of Difluoromethylornithine Chemoprevention on Audiometry Thresholds and Otoacoustic Emissions
Karen J. Doyle, MD, PhD;
Christine E. McLaren, PhD;
Janet E. Shanks, PhD;
Cheryl M. Galus, MA;
Frank L. Meyskens, MD
Arch Otolaryngol Head Neck Surg. 2001;127:553-558.
Objectives To determine the effects of long-term, low-dose difluoromethylornithine
(DFMO) on audiometric thresholds and distortion product otoacoustic emission
(DPOAE) levels in humans.
Design A prospective, randomized, placebo-controlled phase 2 clinical trial
of DFMO in participants with a prior adenomatous colonic polyp.
Setting Academic tertiary care referral center.
Participants One hundred twenty-three volunteer subjects with colorectal polyps and
normal hearing for the frequencies 250 through 2000 Hz.
Interventions Subjects were randomized to receive placebo or oral DFMO at daily dosages
between 0.075 and 0.4 g/m2 of body surface area for 12 months.
Outcome Measures Pure-tone audiometric thresholds for the frequencies 250, 500, 1000,
2000, 3000, 4000, 6000, and 8000 Hz and DPOAE levels were measured at baseline
and 1, 3, 6, 9, and 12 months after starting treatment with DFMO or placebo
and 3 months after cessation of treatment if there was a suggestion of possible
changes at the 12-month measurement.
Results At these low dosages, there was little evidence for shifts in auditory
pure-tone thresholds, and there were no statistically significant shifts in
DPOAE levels. For auditory pure-tone thresholds, there was a subtle, approximately
2- to 3-dB hearing level decrease in hearing sensitivity for the 2 higher
DFMO dosages, but only at the 2 lowest frequencies, 250 and 500 Hz.
Conclusions Administration of low-dose DFMO for 12 months did not produce hearing
loss, in contrast to prior studies that used higher dosages.
From the Department of Otolaryngology (Drs Doyle, Shanks and Ms Galus)
and the Department of Medicine and the Chao Family Comprehensive Cancer Center
(Drs McLaren and Meyskens), University of California, Irvine, and the Department
of Audiology, Veterans Affairs Medical Center, Long Beach, Calif (Dr Shanks).
Corresponding author and reprints: Karen J. Doyle, MD, PhD, Department
of Otolaryngology–Head and Neck Surgery, University of California Davis
Medical Center, 2521 Stockton Blvd, Suite 7200, Sacramento, CA 95817 (e-mail:
karen.doyle{at}ucdmc.ucdavis.edu).
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