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Amelioration of Cisplatin‐Induced ototoxicity by fosfomycin
Author(s) -
Schweitzer Vanessa G.,
Dolan David F.,
Davidson Thomas,
Abrams Gerald E.,
Bs Ronald Snyder
Publication year - 1986
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1288/00005537-198609000-00005
Subject(s) - ototoxicity , nephrotoxicity , cisplatin , fosfomycin , toxicity , pharmacology , organ of corti , medicine , aminoglycoside , hair cell , pathology , chemotherapy , antibiotics , cochlea , chemistry , anatomy , biochemistry
The continued chemotherapeutic application of cisplatin ( cis ‐diamminedichloroplatinum [II]) necessitates reduction of its doselimiting toxicity without decreasing its tumoricidal effect. This research project evaluated the efficacy of fosfomycin, a phosphonic acid antibiotic, in decreasing or ameliorating the ototoxicity (high frequency sensorineural hearing loss) and nephrotoxicity (renal tubular necrosis and interstitial nephritis) of cisplatin. Experimentally, fosfomycin effectively inhibits aminoglycoside‐induced ototoxicity and nephrotoxicity in animals and humans. The efficacy of fosfomycin in blocking platinum‐induced toxicity in the guinea pig was evaluated histologically and functionally using cytocochleography and light microscopy of the organ of Corti and the auditory brain stem evoked response (ABR), and light microscopy of renal corticomedullary tissues, small bowel, liver, lung, and peripheral nerve. The results demonstrate that fosfomycin ameliorates the acute renal tubular necrosis and interstitial nephritis and markedly inhibits the elevation of ABR thresholds and simultaneous outer hair cell loss that can result from cisplatinum administration. Fosfomycin should be considered apotential antidote for the dose‐limiting ototoxicity and nephrotoxicity of cisplatin chemotherapy.