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      Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline

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          Abstract

          Purpose

          To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors.

          Methods

          A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life.

          Results

          A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.

          Recommendations:

          On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted.

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          Most cited references90

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          The European Organization for Research and Treatment of Cancer QLQ-C30: A Quality-of-Life Instrument for Use in International Clinical Trials in Oncology

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            Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial.

            There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy. To determine the effect of duloxetine, 60 mg daily, on average pain severity. Randomized, double-blind, placebo-controlled crossover trial at 8 National Cancer Institute (NCI)-funded cooperative research networks that enrolled 231 patients who were 25 years or older being treated at community and academic settings between April 2008 and March 2011. Study follow-up was completed July 2012. Stratified by chemotherapeutic drug and comorbid pain risk, patients were randomized to receive either duloxetine followed by placebo or placebo followed by duloxetine. Eligibility required that patients have grade 1 or higher sensory neuropathy according to the NCI Common Terminology Criteria for Adverse Events and at least 4 on a scale of 0 to 10, representing average chemotherapy-induced pain, after paclitaxel, other taxane, or oxaliplatin treatment. The initial treatment consisted of taking 1 capsule daily of either 30 mg of duloxetine or placebo for the first week and 2 capsules of either 30 mg of duloxetine or placebo daily for 4 additional weeks. The primary hypothesis was that duloxetine would be more effective than placebo in decreasing chemotherapy-induced peripheral neuropathic pain. Pain severity was assessed using the Brief Pain Inventory-Short Form "average pain" item with 0 representing no pain and 10 representing as bad as can be imagined. Individuals receiving duloxetine as their initial 5-week treatment reported a mean decrease in average pain of 1.06 (95% CI, 0.72-1.40) vs 0.34 (95% CI, 0.01-0.66) among those who received placebo (P = .003; effect size, 0.513). The observed mean difference in the average pain score between duloxetine and placebo was 0.73 (95% CI, 0.26-1.20). Fifty-nine percent of those initially receiving duloxetine vs 38% of those initially receiving placebo reported decreased pain of any amount. Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with placebo for 5 weeks resulted in a greater reduction in pain. clinicaltrials.gov Identifier: NCT00489411.
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              Chemotherapy-induced peripheral neurotoxicity (CIPN): an update.

              The peripheral nervous system can be vulnerable to the toxic action of several drugs since it is not protected as effectively as the central nervous system from noxious exogenous agents. Drug-induced neurotoxicity can affect the nerve fibers or the neuronal bodies (generally the dorsal root ganglia of the primary sensory neurons). Among the neurotoxic drugs antineoplastic agents represent a major clinical problem, given their widespread use and the potential severity of their toxicity. In fact, the peripheral neurotoxicity of antineoplastic agents frequently represents one of their dose-limiting side effects. Moreover, even when antineoplastic agents' peripheral neurotoxicity is not dose-limiting, its onset may severely affect the quality of life of cancer patients and cause chronic discomfort. Among the anticancer chemotherapy drugs, platinum derivates, antitubulins, thalidomide and bortezomib can induce the most severe effects on the peripheral nervous system of the treated patients. Therefore, we will review the features of chemotherapy-induced peripheral neurotoxicity (CIPN) resulting from the administration of these drugs with a focus on new classes of promising antineoplastic agents, such as epothilones and proteasome inhibitors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                Journal of Clinical Oncology
                JCO
                American Society of Clinical Oncology (ASCO)
                0732-183X
                1527-7755
                June 20 2014
                June 20 2014
                : 32
                : 18
                : 1941-1967
                Affiliations
                [1 ]Dawn Hershman, Columbia University Medical Center, New York; Robert Dworkin, University of Rochester, Rochester, NY; Christina Lacchetti and Kate Bak, American Society of Clinical Oncology, Alexandria, VA; Ellen M. Lavoie Smith, University of Michigan, Ann Arbor; Patrick Gavin, Marne, MI; Jonathan Bleeker, Sanford University of South Dakota Medical Center, Sioux Falls, SD; Guido Cavaletti, University of Milano-Bicocca, Monza, Italy; Cynthia Chauhan, Wichita, KS; Antoinette Lavino, Massachusetts General...
                Article
                10.1200/JCO.2013.54.0914
                24733808
                ac08ef09-2cb8-45e4-bb3e-48b6c9f753e9
                © 2014
                History

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