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      The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review

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          Abstract

          Background

          Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction and treatment cessation following the first dose of oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk factor for chronic neuropathy. However, there is underreporting of these parameters during the acute phase (≤ 14 days). This paper systematically reviews the incidence of acute OXIPN and its impact on treatment in the first cycle.

          Methods

          A systematic literature search was performed using PubMed and Medline. Published original articles were included if they described details about prevalence of oxaliplatin-induced acute neuropathy.

          Results

          Fourteen studies, comprised of 6211 patients were evaluated. The majority of patients were treated with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most studies used the National Cancer Institute Common Toxicity Criteria to assess acute neuropathy. Acute neuropathy (Grades 1–4) was the most common event with prevalence ranging from 4–98%, followed by haematological (1.4–81%) and gastrointestinal (1.2–67%) toxicities, respectively. Drug regimens, starting dose of oxaliplatin and neuropathy assessment tools varied across studies. In addition, moderate to severe toxicities were common in patients that received a large dose of oxaliplatin (> 85 mg/m 2) and/ or combined drugs. The majority of studies did not report the factors affecting acute neuropathy namely the range (minimal) doses required to evoke acute neuropathy, patient and clinical risk factors. In addition, there was no systematic reporting of the number of patients subjected to prolonged infusion, dose reduction, treatment delay and treatment cessation during the acute phase.

          Conclusion

          Despite the heterogeneity of studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment tools and study design, a large number of patients developed acute neuropathy. To develop a better preventive and therapeutic guideline for acute/chronic neuropathy, a prospective study should be conducted in a large cohort of patients in relation to drug regimen, starting/ranges (minimal) of doses producing acute neuropathy, treatment compliance, patient and clinical risk factors using a standardised neuropathy assessment tool.

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          Most cited references35

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          Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer.

          To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)-leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m(2)/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m(2), as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. Grade 3 to 4 toxicity from 5-FU-LV occurred in
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            Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial.

            In North America, no effective therapy has been available for patients with progressive metastatic colorectal cancer after front-line treatment with irinotecan, bolus fluorouracil (FU), and leucovorin (IFL). Patients with metastatic colorectal cancer who progressed after IFL therapy were randomly assigned to bolus and infusional FU and leucovorin (LV5FU2), single-agent oxaliplatin, or the combination (FOLFOX4). This planned interim analysis evaluated objective response rate (RR), time to tumor progression (TTP), and alleviation of tumor-related symptoms (TRS) in an initial cohort of patients. Between November 2000 and September 2001, 463 patients from 120 sites in North America were randomly assigned to treatment. FOLFOX4 proved superior to LV5FU2 in all measures of clinical efficacy. Objective RRs determined by an independent radiology panel were 9.9% for FOLFOX4 versus 0% for LV5FU2 (Fisher's exact test, P <.0001). Median TTP was 4.6 months for FOLFOX4 versus 2.7 months for LV5FU2 (two-sided, stratified log-rank test, P <.0001). Relief of TRS occurred in 33% of patients treated with FOLFOX4 versus 12% of patients treated with LVFU2 (chi2 test, P <.001). Single-agent oxaliplatin was not superior to LV5FU2 in any measure of efficacy. Patients treated with FOLFOX4 experienced a higher incidence of clinically significant toxicities than patients treated with LV5FU2, but these toxicities were predictable and did not result in a higher rate of treatment discontinuation or 60-day mortality rate. For patients with metastatic colorectal cancer, second-line treatment with FOLFOX4 is superior to treatment with LVFU2 in terms of RR, TTP, and relief of TRS.
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              A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration.

              The aim of this study was to systematically review the literature on the influence of oxaliplatin administration (e.g. cumulative dose, dose intensity, number of cycles and combination regimen) on the long-term prevalence of oxaliplatin-induced peripheral neuropathy (O-IPN) at least 12 months after termination of chemotherapy.
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                Author and article information

                Contributors
                G.GEBREMEDHN@westernsydney.edu.au
                P.Shortland@westernsydney.edu.au
                D.Mahns@westernsydney.edu.au
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                12 April 2018
                12 April 2018
                2018
                : 18
                : 410
                Affiliations
                [1 ]ISNI 0000 0000 9939 5719, GRID grid.1029.a, School of Medicine, , Western Sydney University, ; Locked Bag 1797, Penrith NSW, Sydney, 2751 Australia
                [2 ]ISNI 0000 0000 9939 5719, GRID grid.1029.a, School of Science and Health, , Western Sydney University, ; Locked Bag 1797, Penrith NSW, Sydney, 2571 Australia
                Author information
                http://orcid.org/0000-0002-2398-7309
                Article
                4185
                10.1186/s12885-018-4185-0
                5897924
                29649985
                bbf10fb2-b066-45a8-9339-96f173ede54d
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 May 2017
                : 6 March 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                colorectal cancer,oxaliplatin,acute neuropathy,chronic neuropathy
                Oncology & Radiotherapy
                colorectal cancer, oxaliplatin, acute neuropathy, chronic neuropathy

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