ASCO updates guidelines on chemotherapy-induced peripheral neuropathy
Chemotherapy-induced peripheral neuropathy is a potentially debilitating consequence of many cytotoxic drugs for the treatment of cancer.
Neuropathies caused by taxanes, platinums, vinca alkaloids, epothilones, eribulin and bortezomib (Velcade, Millennium/Takeda), among other agents, have not been well-defined, and measurement approaches have lacked consistency. However, the use of uniform measurement tools in several recent clinical studies has enabled a more detailed comparison of neuropathies caused by paclitaxel and oxaliplatin.
“Chemotherapy-induced peripheral neuropathy [CIPN] continues to be a major clinical problem,” Charles L. Loprinzi, MD, FASCO, Regis professor of breast cancer research at Mayo Clinic in Rochester, Minnesota, said in an interview with Healio. “A large number of additional randomized clinical trials provided new data from what was available when the first ASCO CIPN guidelines were published.”
Loprinzi served as co-chair of an ASCO expert panel dedicated to updating the society’s guidelines on prevention and management of CIPN among adult cancer survivors, based on these new data. He spoke with Healio about the need for effective treatment for CIPN, the updated guidelines and how the recommendations can be applied in clinical practice.
Question: Why did ASCO update these guidelines?
Answer: CIPN can markedly affect the quality of life of patients. Additionally, it may be detrimental to their cancer outcomes, as it may limit the amount of chemotherapy that clinicians can give. The purpose of this guideline update was to systematically review evidence reported in the literature after publication of the original guideline, compare outcomes among trials, and provide updated guidance on the effectiveness of prevention and treatment options for CIPN in adults who have survived cancer.
Q: Who served on the expert panel?
A: The multidisciplinary expert panel consisted of medical oncologists, pain management nurses, neurologists, clinical pharmacologists, community oncologists, patient representatives and a translational researcher. The panel met via telephone/webinars and communicated through email.
Q: What evidence did the panel review to arrive at the recommendations?
A: The panel conducted a systematic review of PubMed for published, randomized clinical trials with at least 20 patients. Eligible trials were published between Jan. 1, 2013, and Aug. 28, 2019. We conducted an updated search in February 2020. All trials in the review focused on chemotherapy-induced neuropathy, included cancer survivors, and considered neuropathy as an important study outcome.
Q: What was recommended in terms of evaluating drugs known to cause CIPN in patients with underlying neuropathy or predisposing conditions?
A: The panel recommended that clinicians assess the risks and benefits of agents known to cause CIPN among patients with underlying neuropathy and with conditions that predispose to neuropathy, such as diabetes and/or a family or personal history of hereditary neuropathy.
Q: How did the panel arrive at the recommendation against offering acetyl-L-carnitine for the prevention of CIPN among patients with cancer?
A: There have been two published prospective clinical trials looking at this agent as a means of preventing CIPN. One trial was negative, suggesting no difference between acetyl-L-carnitine and placebo. The other trial reported data that supported that patients who received acetyl-L-carnitine did worse than those in the placebo arm.
Q: The panel made no recommendation regarding the use of any of the following to prevent CIPN: acupuncture, cryotherapy, compression therapy, exercise therapy or ganglioside-monosialic acid. Does the lack of recommendation suggest these interventions are not effective for CIPN prevention?
A: No, the lack of recommendation means these agents have neither been proven to be harmful nor beneficial. In fact, preliminary data suggest that cryotherapy, compression therapy, cryo-compression therapy, exercise and a ganglioside-monosialic acid product appear promising and should be investigated further.
Q: The panel advised against offering several agents as CIPN prevention for patients with cancer undergoing treatment with neurotoxic agents. Why was this recommendation made?
A: None of these agents, all of which had been subjects of randomized trials, looked promising. This was an evidence-based guideline with an intermediate quality of evidence and a moderate strength of recommendation.
Q: What did the panel recommend for treatment of CIPN in patients with cancer who are undergoing neurotoxic therapies?
A: Clinicians should assess, and discuss with patients, the appropriateness of dose-delaying, dose-reducing or stopping chemotherapy (or substituting with agents that do not cause CIPN) for patients who develop substantial neuropathy and/or functional nerve impairment.
Q: How should CIPN be treated in patients who have completed neurotoxic treatments?
A: For patients with cancer who experience painful CIPN, clinicians may offer duloxetine. Although recent preliminary evidence suggests potential benefits of exercise, acupuncture and scrambler therapy, definitive studies with larger sample sizes are needed to confirm efficacy and clarify risks. These approaches, however, are appropriate to consider, in clinical practice, noting that proof of benefit is lacking.
For more information:
Charles L. Loprinzi, MD, can be reached at Mayo Clinic, Department of Medical Oncology, 200 First St. SW, Rochester, MN 55905; email: firstname.lastname@example.org.