ASCO Recommends Duloxetine as First-Line Therapy for Chemotherapy-Induced Peripheral Neuropathy

By Lorraine L. Janeczko

September 30, 2021

NEW YORK (Reuters Health) - Duloxetine should be a first-line treatment for chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors, according to updated guidelines from the American Society of Clinical Oncology (ASCO).

"The most important messages from the guidelines are that duloxetine has shown efficacy in the treatment of CIPN and should be considered first-line therapy," said Dr. Benjamin A. Derman of the University of Chicago, who summarized the guidelines in a new report in JAMA with colleague Dr. Andrew M. Davis.

"Also, many agents purported to help with prevention of CIPN do not have robust evidence to support their use in this setting," he told Reuters Health by email. "In particular, acetyl-L-carnitine should not be used for prevention of CIPN."

To update the previous guidelines from 2014, an expert panel appointed by ASCO conducted a literature search for clinical trials published in the intervening years. They identified 45 relevant abstracts that met their selection criteria.

Based on the resulting evidence, the panel recommends that:

- Clinicians may provide duloxetine to patients with painful CIPN (moderate recommendation; intermediate quality of evidence).

- Clinicians should consider delaying, reducing or stopping medication in patients with painful CIPN who are undergoing neurotoxic chemotherapy (moderate recommendation, low quality of evidence).

- Clinicians should not offer the following medications to prevent CIPN: cannabinoids, gabapentin/pregabalin, venlafaxine, vitamin E, vitamin B (moderate recommendation, intermediate quality of evidence).

- Clinicians should discourage the use of acetyl-L-carnitine for CIPN prevention (strong recommendation, high quality of evidence).

The authors acknowledge that, while increased use of duloxetine to treat CIPN may help improve neuropathic pain, it may also cause side effects, including anorexia, weight loss, nausea, headaches and fatigue.

"A multitude of agents available to the practicing clinician may have a reputation for effectively treating or preventing CIPN, but in reality very few of them have evidence to support their use," Dr. Derman said. "These guidelines help clarify which agents should be considered first - and equally important, which should be avoided entirely."

"These guidelines are rooted in the medical literature and are in line with my prior understanding of the evidence and my personal practice," he added. "The key points are clear and concise for the busy clinician who wants to know how to approach CIPN in their patient population."

The authors would like to see more related research.

"The field of CIPN is generally understudied, and many trials that led to the recommendations in these guidelines are smaller studies and used different validated endpoints to describe the impact of the drug in question on CIPN," Dr. Derman said.

"One area that needs further exploration is the use of gabapentinoids (gabapentin/pregabalin) for the treatment of CIPN, given the efficacy of pregabalin for the treatment of CIPN in small studies," he explained.

Dr. Andrew T. Leitner, an anesthesiologist and chief of the Division of Interventional Pain Management at City of Hope Comprehensive Cancer Center in Duarte, California, said, "For a condition as frustratingly prevalent as CIPN, clinicians benefit from this type of updated guidance to avoid prophylactic measures that lack demonstrated efficacy."

"Further, the strong recommendation against prophylactic use of acetyl-L-carnitine adds to the ongoing list of agents that have failed to demonstrate benefit," Dr. Leitner told Reuters Health by email.

"Because there were insufficient data from which to make recommendations," he noted, "further research is needed in both preventive and therapeutic approaches to CIPN that have little risk of harm, such as acupuncture, scrambler therapy, and exercise."

SOURCE: JAMA, online September 21, 2021.