Management of Chemotherapy-Induced Neuropathy

As cancer mortality continues to decline for patients treated with chemotherapy, many survivors live with the late or chronic side effects of these medications. Chemotherapy-induced peripheral neuropathy (CIPN) is a very common post-treatment adverse effect at an estimated incidence of approximately 40%. 

Drugs that pose a particularly high risk for this painful condition include platinum drugs (eg, cisplatin, carboplatin, and oxaliplatin), taxanes, epothilones, plant alkaloids, proteosome inhibitors, and IMiDs. The risk of neuropathy varies according to patient age, dose intensity, cumulative dose and duration of therapy, the particular combination of neurotoxic agents, and presence or absence of peripheral diabetic neuropathy.¹ Patients particularly at risk for CIPN are those who have previous nerve damage related to diabetes mellitus, alcohol use, or an inherited neuropathic condition.² CIPN typically follows a symmetric sensory “glove-and-stocking” distribution. Motor nerve function is rarely affected. Chemotherapy-induced neuropathy may be reversible or irreversible depending on the regimen used and the duration of treatment.¹ The bottom line is that chronic CIPN can be debilitating for patients and pose significant challenges for providers who care for them.  

The American Society of Clinical Oncology (ASCO) has recently issued clinical practice guidelines on the prevention and treatment of CIPN.³ The panel reviewed the available evidence, which included 48 randomized controlled trials originally conducted to evaluate several agents that are used to treat other types of neuropathic pain. The final guidelines do not recommend any pharmacologic approaches to prevent CIPN because of an absence of high-quality evidence. In fact, the guidelines recommended against the use of several agents as preventive treatment, including calcium and magnesium, glutathione, retinoic acid, vitamin E, amifostine, and amitriptyline. The panel noted a lack of evidence but also the potential for harm with these compounds.³

Once CIPN develops, the guidelines recommend the serotonin-norepinephrine reuptake inhibitor duloxetine, citing the strength of evidence as intermediate, evidence of efficacy as moderate, and evidence of harm as low.³ The ASCO panel recommended against the anticonvulsant lamotrigine. The guidelines note that while none of the other studied compounds meet the criteria to be formally recommended for clinical practice at this time, several options could be offered on the basis of their relative safety and given the paucity of other choices available: a tricyclic antidepressant (such as nortriptyline); gabapentin; or a compounded topical gel containing baclofen (10 mg), amitriptyline HCl (40 mg), and ketamine (20 mg).³

As the number of cancer survivors increases, the likelihood that you will treat these patients in a primary care setting also increases. The ASCO guidelines will prove to be a valuable reference for all clinicians treating cancer survivors who live with CIPN.

References:

• Visovsky C. Chemotherapy-induced peripheral neuropathy. Cancer Invest. 2003;21:439–451. http://www.ncbi.nlm.nih.gov/pubmed/?term=Cancer+Invest%2C+2003%2C+21%2C+439%E2%80%93451
• Quasthoff S, Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol. 2002;49:9-17. http://link.springer.com/article/10.1007/PL00007853
• American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2014 Apr 14; [Epub ahead of print]. doi:10.1200/JCO.2013.54.0914. http://jco.ascopubs.org/content/early/2014/04/09/JCO.2013.54.0914.full.pdf