ASCO has released a clinical practice guideline on prevention and treatment of chemotherapy-induced peripheral neuropathy in adult cancer patients, published in the Journal of Clinical Oncology.¹

The guidelines resulted from the efforts of an expert panel, with representation from the fields of medical oncology, community oncology, nursing, pain research, genetics, neurology, pharmacology, patient representation, and guideline methodology. Charles Loprinzi, MD, of the Mayo Clinic, Rochester, Minnesota, and Dawn Hershman, MD, of Columbia University Medical Center, New York, were the panel co-chairs.

The overall incidence of the condition is estimated at close to 40% in patients treated with multiple agents, with reported rates varying according to chemotherapy regimens, duration of exposure, and assessment methods. Regimens associated with higher risk are those including platinum drugs, vinca alkaloids, bortezomib (Velcade), and taxanes.

Clinical Question

The clinical question addressed by the guideline is: What are the optimum prevention and treatment approaches in the management of chemotherapy-induced neuropathies in adult cancer survivors? Guideline development involved a systematic literature search to identify randomized controlled trials in management of chemotherapy-induced peripheral neuropathy. The search identified 1,252 potentially relevant citations, of which 250 were examined in detail, with 48 trials meeting eligibility criteria for use as the evidentiary basis for guideline recommendations. The trials were reported between 1990 and 2013.

A total of 42 studies provided information on 19 different interventions for the prevention of chemotherapy-induced peripheral neuropathy; 6 studies provided information on 6 different agents evaluated in treatment of established neuropathy. The outcomes of interest in analysis of evidence were the incidence and severity of neuropathy, neurophysiologic measures, patient-reported outcomes, and quality of life. The trials generally were small and heterogeneous, often with sample sizes not sufficiently large to detect clinically important differences in outcomes, and usually were not directly comparable due to use of different outcomes and measurements.

Prevention Recommendations

Due to lack of high-quality, consistent evidence, the guidelines do not recommend any agents for use in prevention of chemotherapy-induced peripheral neuropathy. The guidelines specify that clinicians should not offer the following agents for prevention of peripheral neuropathy in cancer patients undergoing treatment with neurotoxic agents:

• Acetyl-L-carnitine (recommendation = strong against, with high strength of evidence, no evidence of efficacy, and high evidence of harm)
• Amifostine (recommendation = moderate against, with intermediate strength of evidence, low evidence of efficacy, and moderate evidence of harm)
• Amitriptyline (recommendation = moderate against, with intermediate strength of evidence, no evidence of efficacy, and moderate evidence of harm)
• Calcium and magnesium for patients receiving oxaliplatin-based chemotherapy (recommendation = moderate against, with high strength of evidence and low evidence of efficacy and harm)
• Diethyldithio-carbamate (recommendation = strong against, with low strength of evidence, no evidence of efficacy, and high evidence of harm
• Glutathione for patients receiving paclitaxel/carboplatin chemotherapy (recommendation = moderate against, with intermediate strength of evidence and low evidence of efficacy and harm)
• Nimodipine (recommendation = strong against, with low strength of evidence, no evidence of efficacy, and moderate evidence of harm)
• Org 2766 (recommendation = moderate against, with intermediate strength of evidence and low evidence of efficacy and harm)
• Retinoic acid (recommendation = moderate against, with low strength of evidence, low evidence of efficacy, and moderate evidence of harm)
• rhuLIF, or emfilermin (recommendation = moderate against, with low strength of evidence, no evidence of efficacy, and low evidence of harm)
• Vitamin E (recommendation = moderate against, with intermediate strength of evidence and low evidence of efficacy and harm.
• Venlafaxine (insufficient information for recommendation, with intermediate strength of evidence and moderate evidence of efficacy and harm) is not recommended for routine clinical use. Although the available data support its potential utility, its use cannot be recommended until additional supporting data become available.
• No recommendations (recommendation = inconclusive, with low strength of evidence and low evidence of efficacy and harm for all) could be made on the use of acetylcysteine, carbamazepine/oxycarbazepine, glutamate, or glutathione for patients receiving cisplatin or oxaliplatin-based chemotherapy, goshajinkigan, or omega-3 fatty acids due to inconclusive evidence of low strength.

Treatment Recommendations

The guidelines provide a moderate strength recommendation for treatment of chemotherapy-induced peripheral neuropathy with duloxetine (intermediate strength of evidence, moderate evidence of efficacy, and low evidence of harm).

No recommendations (recommendation = inconclusive) could be made on the use of the following agents, although the guidelines consider it reasonable to try tricyclic antidepressants, gabapentin, and a topical gel treatment containing baclofen, amitriptyline, and ketamine in select patients:

• Acetyl-L-carnitine (low strength of evidence, low evidence of efficacy, moderate evidence of harm). The guidelines note that an abstract for a phase III trial supported its value, but the trial has yet to be published in a peer-reviewed journal, and a prevention trial suggested worse outcomes with this agent.
• Tricyclic antidepressants (eg, nortryptyline/amitriptyline; intermediate strength of evidence, low evidence of efficacy and harm). The guidelines state that given limited options in chemotherapy-induced peripheral neuropathy and efficacy of these drugs in other neuropathic pain conditions, it is reasonable to try a tricyclic antidepressant (eg, nortriptyline or desipramine) in treatment.
• Gabapentin (intermediate strength of evidence, low evidence of efficacy and harm). The guidelines state that it is reasonable to try this agent in select patients with chemotherapy-induced peripheral neuropathic pain, based on the fact that only one negative randomized trial for this agent was completed and given the efficacy of gabapentin and pregabalin in other forms of neuropathic pain.
• Topical gel treatment containing baclofen (10 mg), amitriptyline (40 mg), and ketamine (20 mg) (intermediate strength of evidence, moderate evidence of efficacy, and low evidence of harm). The guidelines note that a single trial supported a reduction in chemotherapy-induced peripheral neuropathic symptoms with this treatment and that it is reasonable to try the treatment in select patients with neuropathic pain.

For tricyclic antidepressants, gabapentin, and the compounded topical gel, use should occur after discussion with patients about the limited evidence of efficacy in chemotherapy-induced peripheral neuropathy, potential harms and benefits, cost, and patient preferences. The guidelines state that further research on use of these agents in chemotherapy-induced peripheral neuropathy is warranted.

The guidelines make a moderate recommendation against use of lamotrigine (intermediate strength of evidence, no evidence of efficacy, low evidence of harm) in treatment of chemotherapy-induced peripheral neuropathy. ■

Disclosure: For full disclosures of the authors, visit jco.ascopubs.org.

Editor’s note: ASCO has recently adapted guidelines on screening, assessment, and care of anxiety and depressive symptoms, and fatigue. See here and here for more on the newly released guidelines.

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 17, 2014 (early release online).