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Effects Of Different Schedules Of Oxaliplatin Treatment On The Peripheral Nervous System And The Auditory Pathway In The Rat

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The dose-limiting side effect of the second-generation platinum drug oxaliplatin is peripheral neurotoxicity. In the present study we compared the effect on the peripheral nervous system and on the auditory pathway of the rat of four different schedules of oxaliplatin administration using two cumulative doses (36 and 48 mg/kg) and three different intervals between administrations (twice weekly, five consecutive days on alternate weeks or alternate days).

After oxaliplatin treatment platinum was detected in the kidney, dorsal root ganglia (DRG) and sciatic nerve. The neuropathological examination evidenced DRG nucleolar, nuclear and somatic size reduction with DRG nucleolar segregation in all the treated rats. In the sciatic nerves, mild secondary axonopathy occurred. Sensory nerve conduction velocity was reduced after oxaliplatin treatment, while the auditory pathway was unaffected. After a 5-week follow-up period complete recovery of the pathological changes in the DRG and sciatic nerves occurred, although platinum was still detectable in these tissues. In the follow-up period several oxaliplatin-treated rats had abdominal bloating due to local toxicity of the intraperitoneally delivered drug. Conclusion: 1) The least toxic schedules are those used in gr.1 and 2; 2) The shorter the interval between injections, the higher the severity of peripheral neuropathy, related primarily to the cumulative l-OHP dose; 3) The DRG neuronopathy and the nerve damage tend to be reversible; 4) Ototoxicity even with high cumulative doses of oxaliplatin is absent.
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Document Type: Abstract

Affiliations: Ist. Anatomia Umana, Univ. Milano, Milano

Publication date: March 1, 2001

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