Practice guidelines for the prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN) are needed to manage this common adverse event. Following an extensive review of the literature, however, no agents were recommended for prevention of CIPN, and suggestions for management were scant.
The American Society of Clinical Oncology (ASCO) sought to define best practices for treatment of adults who suffer from CIPN and convened an expert panel to review relevant clinical trial results. The authors, led by Dawn Hershman from Columbia University, compiled a list of 42 studies spanning a 23-year period that offered insight into treatment and prevention of CIPN.
No publications provided definitive guidance. Overall, studies tended to have insufficient sample sizes and follow-up, or were inconclusive. Design errors, open-label studies or trials that did not offer placebo comparisons were judged as having potential for bias. In the end, based on published results, the authors compiled a list of 11 established agents that should not be offered to prevent CIPN, including anticonvulsants, antidepressants, vitamins, minerals, supplements and other chemoprotectants. No agents were recommended. One trial involving venlafaxine was inconclusive and merits further investigation.
The group also addressed treatment for patients experiencing CIPN and supported a moderate recommendation of duloxetine, which was effective in cancer-related trials and is used for treatment of diabetic peripheral neuropathy. The panel made no recommendation or endorsement of four other agents shown to be beneficial in small or unpublished studies: acetyl-l-carnitine, tricyclic antidepressants (TCAs); gabapentin or pregabalin; and a compounded gel consisting of baclofen, amitriptyline HCL and ketamine. The clinical practice guideline was published in Journal of Clinical Oncology (2014 Apr 14. [Epub ahead of print], PMID: 24733808).
Robert Taylor, MD|
Chief of Staff
The Ohio State University
Comprehensive Cancer Center–
Arthur G. James Cancer Hospital and
Richard J. Solove Research Institute
Although this is an ambitious and important report, its conclusions are both disappointing and discouraging. As the guideline demonstrates, although we have a fairly good understanding of the causes and mechanisms of CIPN, there is essentially no evidence to support the use of pharmacologic agents to prevent it and very minimal evidence to guide our treatment of it. In the end, the guidelines recommend only duloxetine for treatment of CIPN. However, based on evidence for efficacy in other forms of painful neuropathy and low risk for harm, the guideline suggests that it is reasonable to consider treatment with TCAs; gabapentin or pregabalin; or a topical gel containing baclofen (10 mg), amitriptyline HCL (40 mg) and ketamine (20 mg).
The guideline is most surprising for its silence on the use of opioids for the treatment of CIPN—none of the studies reviewed included treatment with opioids. It is unclear why such studies were excluded; this question was not addressed. This is particularly confusing in that opioids are widely used, and widely believed to be efficacious for the treatment of CIPN. However, if the reason for their exclusion is that they are known to be efficacious, one would assume this would be mentioned in the guideline. Indeed, in the absence of other proven treatments, opioids are likely to remain a mainstay of treatment for pain due to CIPN.
Perhaps the most important parts of the guideline are three sections in the discussion. First, the section labeled “Patient and Clinician Communication” emphasizes the need for patient education and clinician diligence in recognizing and responding to early signs of CIPN, so that, when appropriate, the patient’s chemotherapy regimen can be modified to reduce the risk for progressive CIPN. Second, the “Health Disparities” section reports recent evidence that race may affect the risk for CIPN. Third, the section on “Multiple Chronic Conditions” emphasizes that other conditions, such as diabetes and alcoholism, also may predispose patients to CIPN. Not included in the list of important comorbid conditions are the hereditary neuropathies (which may be subclinical in patients with a family history); it seems likely, and clinical experience supports this, that these also would predispose to CIPN.
In summary, although there is useful information in these guidelines, they are of little help to the clinician faced with the task of caring for a patient suffering with CIPN. Perhaps the main message is that clinicians must communicate well and be vigilant for the early signs of CIPN. Regarding treatment, the guidelines indicate we should try duloxetine first and then consider a TCA or gabapentin or pregabalin. Many clinicians, myself included, would also treat such patients with opioids, and there is nothing in this guideline to warrant changing that practice.
Dr. Taylor reported no relevant financial disclosures.