Longitudinal assessment of oxaliplatin-induced neuropathy

Abstract

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. Neurology ® 2011;77:980-986 GLOSSARY 5-FU ϭ fluorouracil; IENFD ϭ intraepidermal nerve fiber density; NCV ϭ nerve conduction velocity; ON ϭ oxaliplatinassociated neuropathy; PN ϭ peripheral neuropathy; rTNS ϭ reduced total neuropathy score.Oxaliplatin (Sanofi-Aventis; Bridgewater, NJ) is a third-generation platinum derivative that has enhanced inhibition of DNA repair and replication. Oxaliplatin is an antineoplastic agent currently indicated for the treatment of advanced cancer of the colon or rectum.1 A doselimiting toxicity of oxaliplatin is peripheral neuropathy (PN). As oxaliplatin-containing regimens become more successful, the number of long-term survivors will likely increase and neuropathy may emerge as a more important factor limiting quality of life. [1][2][3][4][5] In addition, "stop-and-go" dosing regimens have been adopted in an effort to reduce chronic neuropathy development 1,6,7 and underscores the importance of better understanding this neuropathy. Unpleasant paresthesias in the distal extremities, mouth, and throat are common adverse events associated with acute oxaliplatin administration while a distal length-dependent neuropathy develops with total doses Ն540 -850 mg/m 2 . 2,8The symptoms, functional impairment, and motor axon excitability 9 associate...

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

“…Burakgazi et al (29) have shown that the two best means of evaluating the severity of oxaliplatin neuropathy are through the use of clinical criteria and the distal leg intraepidermal nerve fiber density assay. The latter was not appropriate for our study, since the patients had grade ≥2 neuropathy at the time of inclusion and very likely had diminished nerve fiber density at the start of the study.…”

Neuroprotective effect of saponin rich extract of Acorus calamus L. in rat model of chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain

“…It is characterized by the sensory abnormalities such as unpleasant abnormal sensation (dysesthesia), an increased response to painful stimuli (hyperalgesia), and pain in response to a stimulus that does not normally provoke pain (allodynia) (Burakgazi et al, 2011). Peripheral neuropathic pain is observed frequently in patients with long standing diabetes, cancer, AIDS, leprosy, cervical disc protrusion, foraminotomy, and post-surgical event (Muthuraman and Singh, 2011).…”

Neoadjuvant treatment with cisplatin and S-1 in elderly patients with oesophagogastric adenocarcinoma and locoregional disease: Two case reports and review of the literature

“…Haematological toxicity is reversible, nausea and vomiting are preventable, whereas renal toxicity can be monitored. On the contrary, oxaliplatin-induced polyneuropathy is frequently irreversible and may even worsen after withdrawal of the drug, consistently compromising the quality of life in OAC survivors (26). In our experience, oxaliplatin-induced peripheral polyneuropathy occurs early in the adjuvant (postoperative) phase of perioperative treatment, leading to withdrawal of the drug.…”