title: Longitudinal assessment of oxaliplatin-induced neuropathy.
abstract: OBJECTIVE
  To characterize the natural history of oxaliplatin-associated neuropathy (ON) and determine whether intraepidermal nerve fiber density (IENFD) is a sensitive measure of neuropathy progression. In addition, we sought to assess the potential of ON as a neuroprotection model and gain insight into the relationship between axon loss and neuropathic symptoms.
  
  
  METHODS
  Eight subjects receiving oxaliplatin for advanced colorectal cancer were prospectively followed prior to starting chemotherapy and at 30, 90, 180, and 360 days (180 days after completing treatment). Electrophysiology, punch biopsies, symptom assessment, and examinations with calculation of a reduced total neuropathy score (rTNS) were performed at each time point. Changes over time were assessed through Poisson regression for IENFD and a mixed effects model for rTNS and electrophysiology measures.
  
  
  RESULTS
  The distal leg IENFD, rTNS, peroneal, and sural amplitudes were all significantly reduced over time, while conduction velocity (peroneal and sural) and distal thigh IENFD were not. Measures of axon loss continued to worsen following discontinuation of oxaliplatin. Five of 8 subjects reported prominent symptoms associated with oxaliplatin administration.
  
  
  CONCLUSIONS
  This study demonstrates that oxaliplatin is associated with mild, sensory, and motor axon loss that may not be reversible. Axonal loss was detected by electrophysiology, rTNS, and distal leg IENFD. Several subjects reported prominent sensory symptoms that were not associated with axon loss, and that may or may not represent neuropathy. ON is an attractive paradigm for neuroprotection studies and the distal leg IENFD is an objective measure that requires minimal subject participation or study site expertise.
authors.affiliation: Departments of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: A Z
authors.initials: AZ
authors.lastname: Burakgazi
authors.forename: W
authors.initials: W
authors.lastname: Messersmith
authors.forename: D
authors.initials: D
authors.lastname: Vaidya
authors.forename: P
authors.initials: P
authors.lastname: Hauer
authors.forename: A
authors.initials: A
authors.lastname: Hoke
authors.forename: Michael
authors.initials: M
authors.lastname: Polydefkis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D011115:Polyneuropathies / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin