Stubblefield, M.D., Burstein, H.J., Burton, A.W., Custodio, C.M., Deng, G.E., Ho, M., . . . Von Roenn, J.H. (2009). NCCN task force report: Management of neuropathy in cancer. Journal of the National Comprehensive Cancer Network, 7(Suppl., 5), S1–S26.

This study outlines the common antineoplastic agents known to cause neuropathy and provides information on incidence, onset dosages, the signs and symptoms, and general course and patterns of resolution. Agents identified include platinum compounds, vinca alkaloids, taxanes, bortezomib, ixabepilone, thalidomide, and lenalidomide. In addition to outlining the mechanisms of neuropathy development in cancer, the study discusses neurophysiologic and objective testing, noting that findings on electromyographic (EMG) and nerve conduction studies (NCS) can lag behind clinical symptoms. The study also identifies commonly used physician-based grading systems, including the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) and Eastern Cooperative Oncology Group (ECOG) systems, and notes that these two grading systems lack inter-rater reliability. Patient-based instruments for assessment include the Functional Assessment of Cancer Treatment (FACT) and the Patient Neurotoxicity Questionnaire (PNQ). The authors note that the routine assessment of pain secondary to neuropathy, using instruments such as the Brief Pain Inventory (BPI), is useful.

Routine assessment should be conducted and continued throughout therapy. Key points in assessment that should be included are:

• History, related comorbid conditions, alcohol use, symptoms, pain assessment, time course, and treatment delays or discontinuation from CIPN
• Physical examination
• Patient interview questions regarding sensation of numbness or tingling, pain, bothersome sensations, weakness, difficulty walking, falls, and interference with activities of daily living
• Functional skills testing, such as straight-line walking, name writing, buttoning, pegboard tests, and timed pellet retrieval.

Proposed agents for prevention of CIPN identified include:

• Agents with positive findings: vitamin E, calcium, magnesium, glutamine, glutathione, N-acetylcysteine, oxcarbazepine, xaliproden
• Agents with negative findings: amifostine, nimodipine, Org2766, rhuLIF
• Agents being tested in trials: vitamins B12, B6, acetyl-L-carnititne, alpha lipoic acid

Agents used for pain management:

• Those with negative results in CIPN, including gabapentin, amitriptyline, notriptyline
• Other agents commonly used include duloxetine, 5% lidocaine patch, opioids, tramadol

Current literature is inconclusive on the benefits of neurostimulation in treating CIPN. The authors note that evidence is scarce on efficacy of complimentary and alternative medicine (CAM) therapies and the need for appropriately powered and controlled studies in this area. However, acupuncture was identified as a promising adjunct option. The article also provides safety tips and issues for management of functional deficits in PIN, including situations in which to avoid or discontinue physical training, footwear selection, orthosis, and safety aspects of the household environment. Finally, the article addresses how autonomic neuropathy from chemotherapy occurs, but has not been well documented or studied.

• Limitations include a significant lack of evidence regarding effective management and prevention in this area.
• The review did not describe a search strategy or process to determine the quality of evidence used.

The article provides a comprehensive review of current knowledge about CIPN and common approaches toward assessment, prevention, and management. The authors do not make specific recommendations for treatment, research to validate evaluation tools, and exploration of combinations and scheduling of pain medications. In addition, testing of the safety and effectiveness of therapeutic interventions and dietary supplements are needed.