title: Electroclinical biomarkers of early peripheral neurotoxicity from oxaliplatin.
abstract: Peripheral neuropathy is the principal dose-limiting side effect of chemotherapy with oxaliplatin. Early biomarkers of oxaliplatin-related neuropathy (ON) are important for guiding management and as outcomes for neuroprotective trials. We compared a number of clinical and neurophysiological techniques to identify early features of ON. Median nerve motor excitability testing, nerve conduction studies, vibration perception threshold (VPT) and clinical assessments were carried out on 17 patients and 105 controls. Neuropathy was graded using the total neuropathy score and National Cancer Institute Common Toxicity Criteria scales. Oxaliplatin causes a length-dependent sensory neuropathy. The most sensitive early marker of neuropathy was abnormal VPT in the foot followed by diminished sensory nerve action potential amplitudes. Median nerve excitability studies revealed no biologically significant effects of treatment on motor axons. VPT is an easily applicable and effective marker of neuropathy at low cumulative doses of oxaliplatin. Nerve excitability measures may be useful in predicting ON but motor studies do not reveal early cumulative changes following treatment with the drug.
authors.affiliation: Department of Clinical Neurophysiology, St. Vincent's University Hospital, Dublin 4, Ireland. drjohnmchugh@ireland.com
authors.forename: J C
authors.initials: JC
authors.lastname: McHugh
authors.forename: D
authors.initials: D
authors.lastname: Tryfonopoulos
authors.forename: D
authors.initials: D
authors.lastname: Fennelly
authors.forename: J
authors.initials: J
authors.lastname: Crown
authors.forename: S
authors.initials: S
authors.lastname: Connolly
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D009431:Neural Conduction / Q000502:physiology; D009460:Neurologic Examination / Q000379:methods; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D012684:Sensory Thresholds / Q000502:physiology; D014732:Vibration
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin