Review Chemotherapy-induced peripheral neuropathy: Prevention and treatment strategies Sherry Wolf * , Debra Barton, Lisa Kottschade, Axel Grothey, Charles Loprinzi Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA ARTICLE INFO Article history: Received 22 April 2008 Accepted 29 April 2008 Available online 18 June 2008 Keywords: Neuropathy Chemotherapy Prevention Paclitaxel ABSTRACT Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect of many commonly used chemotherapeutic agents, including platinum drugs, taxanes, epo- thilones and vinca alkaloids, and also newer agents such as bortezomib and lenolidamide. Symptom control studies have been conducted looking at ways to prevent or alleviate established CIPN. This manuscript provides a review of studies directed at both of these areas. New evidence strongly suggests that intravenous calcium and magnesium therapy can attenuate the development of oxaliplatin-induced CIPN, without reducing treatment response. Accumulating data suggest that vitamin E may also attenuate the development of CIPN, but more data regarding its efficacy and safety should be obtained prior to its gen- eral use in patients. Other agents that look promising in preliminary studies, but need sub- stantiation, include glutamine, glutathione, N-acetylcysteine, oxcarbazepine, and xaliproden. Effective treatment of established CIPN, however, has yet to be found. Lastly, paclitaxel causes a unique acute pain syndrome which has been hypothesised to be caused by neurologic injury. No drugs, to date, have been proven to prevent this toxicity. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect of many older commonly used chemotherapeutic agents, including platinum drugs, taxanes, epothilones and vinca alkaloids, but also newer agents such as bortezomib and lenolidamide (Table 1). 1,2 The incidence of CIPN can be variable, but often ranges from 30 to 40% of pa- tients receiving chemotherapy. A number of factors influence the incidence of CIPN in patients receiving neurotoxic chemo- therapy, including patient age, dose intensity, cumulative dose, therapy duration, coadministration of other neurotoxic chemotherapy agents, and pre-existing conditions such as diabetes and alcohol abuse. While symptoms may resolve completely, in some instances CIPN is only partly reversible, and in other cases it does not appear to be reversible at all. 1,3 CIPN can be extremely painful and/or disabling, causing significant loss of functional abilities and decreasing quality of life. Neurotoxic chemotherapeutic agents may cause struc- tural damage to peripheral nerves resulting in aberrant somatosensory processing of the peripheral and/or central nervous system. 4 This resultant peripheral neuropathy can potentially affect both small fibre axons (temperature, pin prick) and large fibre sensory axons (vibration, propriocep- tion). A common clinical course begins with paraesthesias (tingling) and dysaesthesias, commonly located in the toes and fingers. These symptoms then spread proximally to af- fect both lower and upper extremities in a characteristic 0959-8049/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2008.04.018 * Corresponding author: Tel.: +507 538 2098; fax: +507 538 8300. E-mail address: wolf.sherry@mayo.edu (S. Wolf). EUROPEAN JOURNAL OF CANCER 44 (2008) 1507 – 1515 available at www.sciencedirect.com journal homepage: www.ejconline.com