TY - JOUR
T1 - Longitudinal assessment of oxaliplatininduced neuropathy
AU - Burakgazi, A. Z.
AU - Messersmith, W.
AU - Vaidya, D.
AU - Hauer, P.
AU - Hoke, A.
AU - Polydefkis, M.
N1 - Funding Information:
Dr. Burakgazi and Dr. Messersmith reports no disclosures. Dr. Vaidya receives research support from the NIH (NHLBI, NCRR) and the American Heart Association. P. Hauer reports no disclosures. Dr. Hoke performs NCV/EMG studies as part of his clinical practice (15% effort); serves as Associate Editor for Experimental Neurology and on the editorial board of the Journal of PNS; serves as a consultant for Teva Pharmaceutical Industries Ltd.; receives research support from the NIH, the US Department of Defense, the Foundation for Peripheral Neuropathy, the Richard Merkin Foundation, and the Adelson Foundation; has received license fee payments from Johnson and Johnson for technology re: Immortalized DRG neuronal cell line; and has given expert testimony in medico-legal cases. Dr. Polydefkis performs NCV/EMG studies (15% effort) and directs the Johns Hopkins Bayview EMG laboratory; reads punch skin biopsies (0% effort) and directs the Johns Hopkins Cutaneous Nerve Laboratory as part of his clinical practice; and receives research support from the Juvenile Diabetes Research Foundation and the Sidney Kimmel Cancer Center.
PY - 2011/9/6
Y1 - 2011/9/6
N2 - Objectives: 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.
AB - Objectives: 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.
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U2 - 10.1212/WNL.0b013e31822cfc59
DO - 10.1212/WNL.0b013e31822cfc59
M3 - Article
C2 - 21865571
AN - SCOPUS:80055075334
SN - 0028-3878
VL - 77
SP - 980
EP - 986
JO - Neurology
JF - Neurology
IS - 10
ER -