Oxaliplatin-induced neurotoxicity and the development of neuropathy.
The pathophysiology of oxaliplatin-induced neurotoxicity remains unclear, although in vitro studies suggest involvement of voltage-gated Na+ channels. In the present study, clinical assessment was combined with nerve conduction studies (NCS) and nerve excitability studies in 16 patients after completion of oxaliplatin therapy. Chronic neuropathic symptoms persisted in 50% of patients. NCS confirmed abnormalities in symptomatic patients: sensory potentials were significantly low, whereas motor studies remained essentially normal. At 12-month follow-up of symptomatic patients, positive sensory symptoms improved but NCS abnormalities persisted. Cumulative oxaliplatin dose was a predictor of neuropathy, and long-term effects appeared to be minimized by low single-infusion dosages. Nerve excitability measures in symptomatic patients established that axons were of high threshold. Refractoriness was significantly greater in patients (symptomatic group, 56.3 +/- 24.9%; entire patient group, 46.3 +/- 12.5%; controls, 27.1 +/- 1.9%; P < 0.05). Thus, although positive sensory symptoms of oxaliplatin-induced neuropathy improved, negative sensory symptoms and abnormalities of sensory nerve conduction persisted. Differences in nerve excitability measures, particularly refractoriness, support in vitro studies indicating involvement of voltage-gated transient Na+-channel dysfunction in the development of oxaliplatin-induced neurotoxicity.
Krishnan
Arun V
AV
Institute of Neurological Sciences, Prince of Wales Hospital, Sydney, NSW, Australia.
Goldstein
David
D
Friedlander
Michael
M
Kiernan
Matthew C
MC
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002908:Chronic Disease; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D009431:Neural Conduction; D009475:Neurons, Afferent / Q000502:physiology; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D012017:Referral and Consultation
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin