Chemotherapy-induced peripheral neuropathy is a serious yet common side effect of cancer treatment. This devastating complication, which typically manifests as tingling and numbness in the hands and feet, has an enormous influence on patients’ quality of life.
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious yet common side effect of cancer treatment. This devastating complication, which typically manifests as tingling and numbness in the hands and feet, has an enormous influence on patients’ quality of life. Patients with CIPN are often so disabled that they cannot complete simple tasks such as buttoning a shirt, walking normally, or signing their name. Unfortunately, the pathophysiology underlying CIPN remains unclear, although toxic destruction of-and thus a decrease in-intraepidermal nerve endings seems to be associated with the condition. Due to the fact that the pathophysiology of CIPN is complex and not yet fully elucidated, its management remains a challenge for clinicians. Currently available drugs and interventional procedures provide at best only some relief. Most importantly, there is no convincing evidence that any of the currently available drugs prevent or adequately treat this pain syndrome. Consequently, the treatment of CIPN continues to be based on a trial-and-error approach. In this issue of ONCOLOGY, Majithia and colleagues present a clinically relevant review of the prevention, assessment, and treatment of this challenging condition.
The authors should be congratulated for their effort in including not only the various pharmacologic treatment options, but also the relatively new noninvasive procedure called scrambler therapy, which has been shown to have benefit in a few small studies and in our own practice. A recent review by Majithia et al, which one of us (SA) coauthored, reported that scrambler therapy significantly reduced CIPN in 3 out of 4 prospective studies. Further, we have personally had several cases of success, providing concrete evidence of the positive effect of this technology. We believe that scrambler therapy will change the way we treat neuropathic pain-particularly CIPN.
We believe that the following three points are critical to moving the science of CIPN forward:
1) The assessment of CIPN should be standardized. The methods employed should be highly reliable and yet remain a simple bedside clinical tool. In order to evaluate the efficacy of analgesic drugs, it is crucial to be able to adequately assess pain. Unfortunately, the commonly used pain and neuropathy assessment tools are not helpful if there are indeed different pain and neuropathy phenotypes for various chemotherapy drugs.
2) We must recognize that not all CIPNs are “created equal.” The pathophysiology of CIPN associated with one type of chemotherapy might be different from that of the CIPN associated with another type of chemotherapy. Likewise, the treatment of CIPN associated with different types of chemotherapy drugs might also need to be different. The progress-or rather lack of progress-in our ability to understand in depth the differences in mechanisms for the different types of neuropathic pain syndromes, together with pharmacogenetic and genetic variations in individual patients, makes it very difficult to target the problem in a given patient.
3) Well-thought-out and better-designed, meaningful studies are needed-not only randomized controlled trials, but also observational studies with a sufficient number of subjects to achieve not just statistical significance, but, most importantly, clinical significance. Most of the studies discussed in this review had a small number of subjects and were of relatively short duration.
In summary, even though the review by Majithia and colleagues does not present a new approach, aside from its description of scrambler therapy, the authors have nicely reviewed the evidence (or lack thereof) for the prevention, assessment, and treatment of CIPN. Assessment of CIPN remains nonstandardized and relies heavily on the patient and on the experience of the clinician evaluator. There is still no convincing evidence that any measures or drugs reliably prevent or treat CIPN; thus, choosing treatment drugs continues to be by trial and error. In this regard, we would suggest that some of the agents that Majithia et al have categorized as having “no evidence of efficacy” (or “no good evidence . . .”) may still provide benefit for a given patient. Even though randomized trials may not have supported some agents, they should not be summarily written off. Lastly, some of the interventional procedures, such as spinal cord stimulation, are very expensive and risky, and good evidence that they can effectively treat CIPN is lacking. Finally, we hope that well-designed prospective studies (both randomized controlled trials and observational studies) will be conducted in the future so that we might have a better understanding of the mechanism(s) of CIPN, do better assessment, and be able to offer affected patients innovative evidence-based treatment options.
Financial Disclosure:The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Kim JH, Dougherty PM, Abdi S. Basic science and clinical management of painful and non-painful chemotherapy-related neuropathy. Gynecol Oncol. 2015;136:453-9.
2. Majithia N, Loprinzi CL, Smith TJ. New practical approaches to chemotherapy-induced neuropathic pain: prevention, assessment, and treatment. Oncology (Williston Park). 2016;30:1020-9.
3. Majithia N, Smith TJ, Coyne PJ, et al. Scrambler therapy for the management of chronic pain. Support Care Cancer. 2016;24:2807-14.