Guidelines for Chemotherapy-Induced Neuropathy: The Known Unknowns


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Harold J. Burstein, MD, PhD

The tools exist, the problem [of chemotherapy-induced neuropathy] is prevalent, and it is time to insist upon a robust series of clinical investigations to rapidly sort out promising agents and strategies to minimize this burden in the cancer community.

—Harold J. Burstein, MD, PhD

It is a tribute to the advances in supportive care that peripheral neuropathy, along with fatigue, has become the most vexing management challenge in cancer patients receiving chemotherapy. The successes of modern antiemetic regimens and white blood cell growth factor support have radically altered the short-term side-effect profiles of chemotherapy. Vomiting and neutropenic fever have become far less frequent as major complications for patients receiving chemotherapy, and a variety of interventions are available to minimize the symptoms. Instead, the subacute and chronic syndromes of chemotherapy-induced fatigue and peripheral neuropathy have become the most challenging, and frequently, treatment-limiting, consequences.

Unrelenting Problem

Many of the most common chemotherapy agents used in the treatment of the most common cancers—eg, taxanes for breast, lung, prostate, and gynecologic tumors, oxaliplatin for colon cancer, platinum-based chemotherapy for lung and gynecologic cancers—are strongly associated with risks of peripheral neuropathy. Newer agents such as bortezomib (Velcade), used in multiple myeloma, and brentuximab vedotin (Adcetris) used in certain lymphomas, can also cause neuropathy.

Neuropathy can be an unrelenting problem that ranges from annoying discomfort to major impediment to daily activities, and can last long beyond actual treatment. Neuropathy often prompts oncologists to modify treatment dosing or scheduling when it is brought to their attention. There is, of course, no x-ray or lab test for neuropathy, and the strong suspicion is that the prevalence and seriousness of neuropathy—like so many patient-reported outcomes—is underappreciated by clinicians caring for cancer patients.

Valuable Document

Given the significance and prevalence of chemotherapy-induced neuropathy, it is important for clinicians to understand how they might prevent or treat the condition so as to reduce suffering among our patients receiving chemotherapy. The new ASCO guideline on chemotherapy-induced peripheral neuropathy,1 published in the Journal of Clinical Oncology and reviewed in this issue of The ASCO Post, is a valuable document that brings together the known information on how to manage neuropathy in cancer patients.

Alas, what we mostly know about managing chemotherapy-induced neuropathy is how little we know. The evidence for treatment recommendations? “Small” trials with “insufficient sample sizes,” inconsistent definitions of outcomes and treatment endpoints, and a scientific foundation for pathophysiology and pharmacology that is disappointing. In the end, not a single agent could be recommended for preventing chemotherapy-induced neuropathy, and only one (duloxetine) could be recommended as treatment based on a single randomized trial.

One purpose of a guideline is to articulate the “don’ts” along with the “dos” and for this reason, the ASCO guideline is quite helpful. Given the lack of compelling data for preventing or treating peripheral neuropathy due to chemotherapy, patients often try a lot of different interventions based on anecdotes, claims made in health stores, and other incomplete sources of information. The guideline is forceful in recommending against a number of such agents, including nutritional supplements like acetyl-L-carnitine and glutathione, various vitamins and minerals, and a variety of prescription medicines. The guideline appropriately cautions clinicians and patients about the limited roles for gabapentin and tricyclic antidepressants, agents with relatively small benefits and substantial potential side effects, in the treatment of chemotherapy-induced neuropathy.

Clear Message

There is a clear message that it is time to take the gloves off in the battle against chemotherapy-induced neuropathy. As the guideline makes apparent, there are appropriate, clinically validated methods for assessing the impact of treatments for neuropathy in cancer patients. The tools exist, the problem is prevalent, and it is time to insist upon a robust series of clinical investigations to rapidly sort out promising agents and strategies to minimize this burden in the cancer community.

The ASCO guideline has mapped out for us the “known unknowns.” Hopefully, it will also create a commitment among patient advocates, clinical investigators, foundations and support groups, and pharmaceutical partners to transform this domain of supportive care in the same way that antiemetic and growth factor innovations tackled nausea/vomiting and neutropenia. When the updated ASCO guideline comes forward in a few years, we will expect that there will be a lot fewer unknowns and a lot more knowns in management of chemotherapy-induced neuropathy. ■

Disclosure: Dr. Burstein reported no potential conflicts of interest.

Reference

1. Hershman DL, Lacchetti C, Dworkin RH, et al: Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. April 14, 2014 (early release online).

 

Dr. Burstein is Associate Professor of Medicine at Harvard Medical School, staff physician at Brigham and Women’s Hospital, and a medical oncologist at Dana-Farber Cancer Institute, Boston.

 


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