This Article  • References  • Full text PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

-Difluoromethylornithine Ototoxicity

Chemoprevention Clinical Trial Results

Thomas R. Pasic, MD; Dennis Heisey, PhD; Richard R. Love, MD

Arch Otolaryngol Head Neck Surg. 1997;123(12):1281-1286.

Abstract
Objectives
To determine the effects of low-dose oral eflornithine hydrochloride (difluoromethylornithine [DFMO]) administration on hearing and to identify factors that influence those effects.

Design
Combined data from 2 studies: a prospective, randomized phase 1 clinical trial of eflornithine (n=26 subjects) and a prospective, randomized, placebocontrolled phase 2 clinical trial of eflornithine (n=40 subjects).

Setting
Ambulatory academic tertiary care referral center.

Participants
Sixty-six volunteer subjects who had previously treated bladder, prostate, or colon cancer with no current evidence of neoplastic disease, or who were healthy individuals at increased risk for colon cancer, all without need of hearing amplification.

Interventions
Subjects were randomized to receive oral eflornithine at daily doses between 0.5 and 3 g per square meter of body surface area (g/m²) for 6 to 12 months (phase 1 study) or randomized to receive placebo or eflornithine, 0.5 g/m² for 12 months (phase 2 study).

Outcome Measures
Auditory thresholds were measured before, during, and after eflornithine administration. Auditory thresholds and threshold shifts were evaluated with regard to eflornithine dose, serologic variables, and demographic factors.

Results
Predictable shifts in auditory thresholds occurred following administration of eflornithine. As the daily dose of eflornithine increased, the magnitude and incidence of threshold shift increased, and the time until onset of threshold shift decreased. Threshold changes were greater in the lower frequencies than in the higher frequencies. Subjects' sex, age, and renal function had no effect on eflornithineassociated threshold shifts. Threshold shifts were reversible after eflornithine treatment was discontinued.

Conclusions
Administration of eflornithine is associated with a predictable shift in auditory thresholds. The magnitude and incidence of threshold shift correlate with the daily eflornithine dose.

Arch Otolaryngol Head Neck Surg. 1997;123:1281-1286

Author Affiliations
From the Division of Otolaryngology—Head and Neck Surgery (Dr Pasic), and the Departments of Surgery (Dr Heisey) and Medicine (Dr Love), University of Wisconsin, Madison.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Longitudinal Assessment of Air Conduction Audiograms in a Phase III Clinical Trial of Difluoromethylornithine and Sulindac for Prevention of Sporadic Colorectal Adenomas
McLaren et al.
Cancer Prevention Research 2008;1:514-521.
ABSTRACT | FULL TEXT  

Effect of dietary green tea extract and aerosolized difluoromethylornithine during lung tumor progression in A/J strain mice
Anderson et al.
Carcinogenesis 2008;29:1594-1600.
ABSTRACT | FULL TEXT  

Functional Consequences of Polyamine Synthesis Inhibition by L-{alpha}-Difluoromethylornithine (DFMO): CELLULAR MECHANISMS FOR DFMO-MEDIATED OTOTOXICITY
Nie et al.
J. Biol. Chem. 2005;280:15097-15102.
ABSTRACT | FULL TEXT  

Irreversible Ototoxicity Associated with Difluoromethylornithine
Lao et al.
Cancer Epidemiol. Biomarkers Prev. 2004;13:1250-1252.
ABSTRACT | FULL TEXT  

Effects of Difluoromethylornithine Chemoprevention on Audiometry Thresholds and Otoacoustic Emissions
Doyle et al.
Arch Otolaryngol Head Neck Surg 2001;127:553-558.
ABSTRACT | FULL TEXT