Peripheral neuropathy is one of the most prominent chronic side effects of chemotherapy and can linger for years, causing discomfort as well as impaired functionality and quality of life. Yet oncologists have struggled to identify definitive treatment and prevention strategies.
In an effort to help clinicians stave off and manage chemotherapy-induced peripheral neuropathy, ASCO recently updated its consensus guideline for chemotherapy-induced peripheral neuropathy among survivors of adult cancers.1
Getting Ahead of the Problem
Charles L. Loprinzi, MD, FASCO
Dawn L. Hershman, MD, MS, FASCO
According to guideline Co-Chairs of the expert panel Charles L. Loprinzi, MD, FASCO, of the Mayo Clinic, Rochester, Minnesota, and Dawn L. Hershman, MD, MS, FASCO, of Columbia University Herbert Irving Comprehensive Cancer Center, there have been 42 new clinical trials since the 2014 guideline for chemotherapy-induced peripheral neuropathy in adult patients with cancer, underscoring the need to revisit the current state of the science.
“Chemotherapy-induced peripheral neuropathy is clearly one of the more troublesome side effects of many different types of agents we use to treat cancer,” Dr. Hershman said. “[Although] there have been a lot of different clinical trials over time, we really haven’t made huge progress in terms of identifying [effective] agents or strategies for either prevention or treatment.”
As such, the expert panel reviewed the most recent literature, as well as the methodologies of new trials and developed recommendations in three aspects of clinical care for chemotherapy-induced peripheral neuropathy: prevention, treatment while patients are receiving chemotherapy, and treatment after chemotherapy.
Preventive Measures Under Study
“[Regarding prevention], what we said in 2014 was there was no evidence that anything works in this area despite multiple studies, and that still is the answer now,” Dr. Loprinzi said. “We have no evidence that something works to prevent neuropathy from happening, other than not giving the chemotherapy. However, there is some suggestive evidence there may be benefit from [certain preventive measures].”
Such preventive measures, he said, include cryotherapy, which may reduce peripheral nerve damage by using cold temperatures to constrict blood flow; compression therapy, which similarly restricts blood vessels through applied pressure (eg, placement of tight surgical gloves on the hands); and exercise. Dr. Loprinzi emphasized that these options are not yet supported by convincing evidence and require more data, but they are used in clinical practice, by some clinicians, and are not likely to cause harm to many patients.
“Lastly, regarding prevention, there are now data to strongly support that acetyl-L-carnitine could be harmful,” Dr. Loprinzi added. “So, it should be avoided.”
Weighing Treatment Options
Given that prevention of chemotherapy-induced peripheral neuropathy is not always possible, effective interventions are key to helping patients preserve functioning and quality of life. However, few trials have examined the management of chemotherapy-induced peripheral neuropathy during chemotherapy, leaving oncologists with few options beyond weighing the potential benefit of continuing treatment once chemotherapy-induced peripheral neuropathy occurs. For example, if a patient is scheduled to receive 12 cycles of chemotherapy but has significant chemotherapy-induced peripheral neuropathy after 8 cycles, the panel recommends clinicians consider how much additional benefit may, or may not, be conferred by exposing the patient to the remaining 4 cycles.
Chemotherapy-induced peripheral neuropathy after chemotherapy had comparatively more evidence, although additional data are needed. In fact, the only recommended treatment from the panel was duloxetine. Exercise, acupuncture, and scrambler therapy (ie, cutaneous electrostimulation) were classified as unproven yet reasonable additional choices to consider.
Awareness of Limitations in the Literature
Drs. Hershman and Loprinzi both noted that although research on chemotherapy-induced peripheral neuropathy has increased since the original guideline was released, the panel was careful to scrutinize the quality of these studies, which explains in part why these latest recommendations do not differ significantly from their predecessor. “One real advantage of putting together this guideline is it gives us an opportunity to review what works and what doesn’t work, but also the methods by which these trials are being done, and inform the community in terms of which strategies are more rigorous and have more fidelity,” Dr. Hershman said.
Dr. Hershman added that research on outcome measures and patient experience does appear to have improved over time. However, clinicians should still be aware of limitations in the literature.
“Despite the fact there are many agents tested and not shown to be efficacious, people still use them,” noted Dr. Hershman. “We really hope the guideline helps inform which [agents] people should use but also which they shouldn’t use for the prevention and treatment of chemotherapy-induced peripheral neuropathy.”
DISCLOSURE: Dr. Loprinzi has served as a consultant or advisor to Asahi Kasei, Disarm Therapeutics, Metys Pharmaceuticals, Mitsubishi Tanabe Pharma, NKMax, OnQuality Pharmaceuticals, and PledPharma; has received institutional research funding from Bristol Myers Squibb; and has held other relationships with Hologic/Cynosure. Dr. Hershman has served as a consultant or advisor to AIM Specialty Health. For full disclosures of other panel members, visit ascopubs.org.
1. Loprinzi CL, Lacchetti, C, Bleeker J, et al: Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: ASCO guideline update. J Clin Oncol. July 14, 2020 (early release online).
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, July 16, 2020. All rights reserved.