Recommendations for cancer prevention trials using potentially ototoxic test agents.
OBJECTIVE
Preventive oncology applies pharmacologic agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy, a process that may require administration of agents over long periods of time. Although ototoxicity may be a tolerable side effect of anticancer or antimicrobial therapy, even modest ototoxicity may not be acceptable in agents developed for preventive oncology that are routinely administered to subjects who neither are, nor necessarily will become, clinically ill.


METHODS
Age-related shifts in hearing may occur over the course of longterm or open-ended therapy; consequently, age-adjusted norms enable researchers to better distinguish hearing loss caused by drugs from that caused by aging. Norms for hearing sensitivity are derived from the Baltimore Longitudinal Study of Aging and are the basis for the proposed audiologic monitoring recommendations.


RESULTS
Audiologic monitoring recommendations are presented that standardize patient selection, adverse event reporting, posttreatment follow-up, and audiologic testing for potentially ototoxic investigational agents.


CONCLUSIONS
These recommendations are applicable to trials of investigational agents as well as various classes of drugs used in routine clinical care.
Hearing Section, Neuro-Otology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
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Shotland
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Ondrey
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Mayo
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Viner
D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001299:Audiometry; D018890:Chemoprevention; D003638:Deafness / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009369:Neoplasms / Q000517:prevention & control; D018579:Patient Selection; D017410:Practice Guidelines as Topic
D000970:Antineoplastic Agents