Irreversible ototoxicity associated with difluoromethylornithine

Christopher D. Lao, Patricia Backoff, Lawrence I. Shotland, Deborah McCarty, Tracy Eaton, Frank G. Ondrey, Jaye L. Viner, Stuart Jon Spechler, Ernest T. Hawk, Dean E. Brenner

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Difluoromethylornithine (DFMO) is a potent, irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the synthesis of polyamines that promote cellular proliferation. DFMO has been tested as a potential cancer therapeutic and chemopreventive agent in clinical trials. Reversible hearing loss is a recognized toxicity of DFMO that usually occurs at doses above 2 g/m2/d, and generally when the cumulative dose exceeds 250 g/m 2. In a recently completed Barrett's esophagus chemoprevention trial, a participant developed a 15-dB decrease in hearing at frequencies of 250, 2,000, and 3,000 Hz in the right ear and a ≥20-dB decrease in hearing at 4,000 to 6,000 Hz in the left ear after taking 0.5 g/m2/d DFMO for approximately 13 weeks (cumulative dose of 45 g/m2). The threshold shifts persisted 7 months after DFMO was discontinued. There was no obvious impact on the participant's clinical hearing, but these findings were consistent with irreversible hearing loss. This is the first case reported of irreversible ototoxicity in a clinical trial participant receiving DFMO and, thus, trial participants should be made aware of this small but important risk.

Original languageEnglish (US)
Pages (from-to)1250-1252
Number of pages3
JournalCancer Epidemiology Biomarkers and Prevention
Volume13
Issue number7
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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