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      Overview of neuropathy associated with taxanes for the treatment of metastatic breast cancer

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          Abstract

          Taxanes are an established option in the standard treatment paradigm for patients with metastatic breast cancer (MBC). Neuropathy is a common, dose-limiting side effect of taxane therapy that is often managed by dose reductions and delays. The severity, time to onset, and improvement in neuropathy are important considerations for patient management and vary among currently approved taxanes. The rate of grade ≥3 neuropathy with taxanes has been shown to be dose and schedule dependent; however, time to improvement to grade ≤1 is typically shorter for nab-paclitaxel than for other taxanes in patients with MBC. Many tools for assessing patient-reported neuropathy exist. Because MBC is incurable and patient quality of life must be critically considered when making treatment decisions, there is a need for more prospective trials to assess patient-reported neuropathy. Validated predictors of taxane-related neuropathy may play an important role in treatment decisions in the future. This review will focus on the toxicity profile (i.e., neuropathy) of each of the taxanes used in the treatment of MBC, will provide updates on tools used for the assessment of neuropathy, and will highlight newly discovered predictors of taxane-related neuropathy.

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          Most cited references71

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          Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer.

          ABI-007, the first biologically interactive albumin-bound paclitaxel in a nanameter particle, free of solvents, was compared with polyethylated castor oil-based standard paclitaxel in patients with metastatic breast cancer (MBC). This phase III study was performed to confirm preclinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with standard paclitaxel. Patients were randomly assigned to 3-week cycles of either ABI-007 260 mg/m(2) intravenously without premedication (n = 229) or standard paclitaxel 175 mg/m(2) intravenously with premedication (n = 225). ABI-007 demonstrated significantly higher response rates compared with standard paclitaxel (33% v 19%, respectively; P = .001) and significantly longer time to tumor progression (23.0 v 16.9 weeks, respectively; hazard ratio = 0.75; P = .006). The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with standard paclitaxel (9% v 22%, respectively; P < .001) despite a 49% higher paclitaxel dose. Febrile neutropenia was uncommon (< 2%), and the incidence did not differ between the two study arms. Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the standard paclitaxel arm (10% v 2%, respectively; P < .001) but was easily managed and improved rapidly (median, 22 days). No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time. ABI-007 demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel in this patient population. The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC.
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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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              The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study.

              The magnitude of the health problem from diabetic neuropathies remains inadequately estimated due to the lack of prospective population-based studies employing standardized and validated assessments of the type and stage of neuropathy as compared with background frequency. All Rochester, Minnesota, residents with diabetes mellitus on January 1, 1986, were invited to participate in a cross-sectional and longitudinal study of diabetic neuropathies (and also of other microvascular and macrovascular complications). Of 64,573 inhabitants on January 1, 1986 in Rochester, 870 (1.3%) had clinically recognized diabetes mellitus (National Diabetes Data Group criteria), of whom 380 were enrolled in the Rochester Diabetic Neuropathy Study. Of these, 102 (26.8%) had insulin-dependent diabetes mellitus (IDDM), and 278 (73.2%) had non-insulin-dependent diabetes mellitus (NIDDM). Approximately 10% of diabetic patients had neurologic deficits attributable to nondiabetic causes. Sixty-six percent of IDDM patients had some form of neuropathy; the frequencies of individual types were as follows: polyneuropathy, 54%; carpal tunnel syndrome, asymptomatic, 22%, and symptomatic, 11%; visceral autonomic neuropathy, 7%, and other varieties, 3%. Among NIDDM patients, 59% had various neuropathies; the individual percentages were 45%, 29%, 6%, 5%, and 3%. Symptomatic degrees of polyneuropathy occurred in only 15% of IDDM and 13% of NIDDM patients. The more severe stage of polyneuropathy, to the point that patients were unable to walk on their heels and also had distal sensory and autonomic deficits (stage 2b) occurred even less frequently--6% of IDDM and 1% of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Contributors
                (480) 256-4607 , edgardo.rivera@bannerhealth.com
                Journal
                Cancer Chemother Pharmacol
                Cancer Chemother. Pharmacol
                Cancer Chemotherapy and Pharmacology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0344-5704
                1432-0843
                18 January 2015
                18 January 2015
                2015
                : 75
                : 4
                : 659-670
                Affiliations
                Banner MD Anderson Cancer Center, 2946 E. Banner Gateway Drive, Gilbert, AZ 85234 USA
                Article
                2607
                10.1007/s00280-014-2607-5
                4365177
                25596818
                5df87ef6-2138-4c62-bb70-53f1b2384cb3
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 28 March 2014
                : 7 October 2014
                Categories
                Review Article
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2015

                Oncology & Radiotherapy
                taxanes,neuropathy,metastatic breast cancer,nab-paclitaxel,docetaxel,paclitaxel

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