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 ba...

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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

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling pain condition resulting from chemotherapy for cancer. Severe acute CIPN may require chemotherapy dose reduction or cessation. There is no effective CIPN prevention strategy; treatment of established chronic CIPN is limited, and the prevalence of CIPN is not known. Here we used a systematic review to identify studies reporting the prevalence of CIPN. We searched Embase, Medline, CAB Abstracts, CINAHL, PubMed central, Cochrane Library, and Web of Knowledge for relevant references and used random-effects meta-regression to estimate overall prevalence. We assessed study quality using the CONSORT and STROBE guidelines, and we report findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. We provide a qualitative summary of factors reported to alter the risk of CIPN. We included 31 studies with data from 4179 patients in our analysis. CIPN prevalence was 68.1% (57.7-78.4) when measured in the first month after chemotherapy, 60.0% (36.4-81.6) at 3months and 30.0% (6.4-53.5) at 6months or more. Different chemotherapy drugs were associated with differences in CIPN prevalence, and there was some evidence of publication bias. Genetic risk factors were reported in 4 studies. Clinical risk factors, identified in 4 of 31 studies, included neuropathy at baseline, smoking, abnormal creatinine clearance, and specific sensory changes during chemotherapy. Although CIPN prevalence decreases with time, at 6months 30% of patients continue to suffer from CIPN. Routine CIPN surveillance during post-chemotherapy follow-up is needed. A number of genetic and clinical risk factors were identified that require further study.

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Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

The purpose of the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline is to provide recommendations to assist primary care and other clinicians in the care of female adult survivors of breast cancer. A systematic review of the literature was conducted using PubMed through April 2015. A multidisciplinary expert workgroup with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology, and nursing was formed and tasked with drafting the Breast Cancer Survivorship Care Guideline. A total of 1,073 articles met inclusion criteria; and, after full text review, 237 were included as the evidence base. Patients should undergo regular surveillance for breast cancer recurrence, including evaluation with a cancer-related history and physical examination, and should be screened for new primary breast cancer. Data do not support performing routine laboratory tests or imaging tests in asymptomatic patients to evaluate for breast cancer recurrence. Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy. Recommendations provided in this guideline are based on current evidence in the literature and expert consensus opinion. Most of the evidence is not sufficient to warrant a strong evidence-based recommendation. Recommendations on surveillance for breast cancer recurrence, screening for second primary cancers, assessment and management of physical and psychosocial long-term and late effects of breast cancer and its treatment, health promotion, and care coordination/practice implications are made.This guideline was developed through a collaboration between the American Cancer Society and the American Society of Clinical Oncology and has been published jointly by invitation and consent in both CA: A Cancer Journal for Clinicians and Journal of Clinical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Cancer Society or the American Society of Clinical Oncology.

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American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline

With a 3-fold increase in the number of cancer survivors noted since the 1970s, there are now over 28 million cancer survivors worldwide. Accordingly, there is a heightened awareness of long-term toxicities and the impact on quality of life following treatment in cancer survivors. This review will address the increasing importance and challenge of chemotherapy-induced neurotoxicity, with a focus on neuropathy associated with the treatment of breast cancer, colorectal cancer, testicular cancer, and hematological cancers. An overview of the diagnosis, symptomatology, and pathophysiology of chemotherapy-induced peripheral neuropathy will be provided, with a critical analysis of assessment strategies, neuroprotective approaches, and potential treatments. The review will concentrate on neuropathy associated with taxanes, platinum compounds, vinca alkaloids, thalidomide, and bortezomib, providing clinical information specific to these chemotherapies. CA Cancer J Clin 2013;63:419-437. ©2013 American Cancer Society, Inc.

https://onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21204

Chemotherapy-induced peripheral neurotoxicity: a critical analysis.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. Approximately 30 to 40% of patients treated with neurotoxic chemotherapy will develop CIPN, and there is considerable variability in its severity between patients. It is often sensory-predominant with pain and can lead to long-term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents. Ann Neurol 2017;81:772-781.

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Chemotherapy-induced peripheral neuropathy: A current review

Importance There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy. Objective To determine the effect of duloxetine, 60 mg daily, on average pain severity. Design, Setting, and Patients 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. Interventions 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. Main Outcome Measures 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. Results 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. Conclusion and Relevance 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. Trial Registration clinicaltrials.gov Identifier: NCT00489411

https://jamanetwork.com/journals/jama/articlepdf/1674238/joc130031_1359_1367.pdf

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

CRA9013 Background: CALGB 170601 was a randomized, placebo-controlled phase III trial to determine whether duloxetine reduces painful chemotherapy-induced peripheral neuropathy (CIPN). The secondary study endpoint was treatment-related adverse events. Methods: The study used a double-blinded placebo-controlled crossover design with equally weighted randomization to one of two arms. Arm A participants received duloxetine followed by placebo. Arm B participants received placebo followed by duloxetine. The initial and crossover periods each consisted of six weeks of drug/placebo followed by one week of washout. Randomization was stratified by neurotoxic agent and high risk for developing painful CIPN. Eligible patients were 18 years or older with an average CIPN pain score > 4/10 attributed to prior single agent taxane or platinum treatment. Participants took one capsule daily (30mg) for one week, and then two capsules (60mg) daily for four additional weeks. Participants completed the Brief Pain Inventory-Sh...

Chetaye Knox

Papers

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

CALGB 170601: A phase III double blind trial of duloxetine to treat painful chemotherapy-induced peripheral neuropathy (CIPN).