Delayed, reversible hearing loss caused by difluoromethylornithine (DFMO)

Area of Science:

• Ototoxicology
• Pharmacology
• Neuroscience

Background:

• Difluoromethylornithine (DFMO) is an experimental anticancer drug with known ototoxic properties.
• Understanding the ototoxic effects of DFMO is crucial for its clinical application and patient safety.

Purpose of the Study:

• To establish a DFMO dose and schedule causing significant hearing loss (HL) in newborn gerbils.
• To compare HL in gerbils receiving DFMO versus saline placebo.
• To assess the reversibility of DFMO-induced HL after treatment cessation.

Main Methods:

• Prospective, non-randomized experimental design utilizing placebo controls.
• Click-evoked auditory brainstem response (ABR) testing in Mongolian gerbils.
• Daily subcutaneous injections of DFMO or saline over varying schedules, with recovery assessment in one experiment.

Main Results:

• An 18-day DFMO regimen (1 g/kg/day) resulted in click thresholds of 25–65 dB nHL, compared to 5–20 dB nHL in saline controls.
• Statistically significant differences in hearing thresholds were observed.
• Hearing thresholds returned to normal levels (5–20 dB nHL) after a 3-week recovery period post-DFMO treatment.

Conclusions:

• DFMO induces mild to moderate hearing loss in neonatal gerbils.
• The hearing impairment caused by DFMO is reversible upon drug discontinuation.
• These findings have implications for managing potential ototoxicity in patients receiving DFMO therapy.