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      Emerging Treatment Options For Cancer-Associated Cachexia: A Literature Review

      review-article
      1
      Therapeutics and Clinical Risk Management
      Dove
      cancer cachexia, physical function, anamorelin, multimodal intervention

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          Abstract

          Cachexia is a disease that has been recognized since antiquity; however, research in this area has recently increased. Promising new agents, including anamorelin hydrochloride, have been tested in large randomized controlled studies, and multidrug as well as multimodal approaches have been proposed as having the potential to improve outcomes in patients with cancer cachexia. However, standard treatment remains elusive. This review summarizes the current literature on treatment of cancer-associated cachexia, showing that there are challenges associated with conducting clinical trials in such patients. First, poor recruitment, retention, and compliance among cachectic patients cause research delays. Second, the lack of consensus regarding clinically meaningful endpoints impedes standardization of study designs and results. Further consideration is needed to identify the most suitable study design and endpoints, which can lead to the development of pharmacological and nonpharmacological interventions that improve patients’ prognosis and outcomes.

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          Most cited references73

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          A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy.

          PGC-1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise but has no effects on muscle strength or hypertrophy. We have identified a form of PGC-1α (PGC-1α4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1α4 is highly expressed in exercised muscle but does not regulate most known PGC-1α targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1α4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1α4 show increased muscle mass and strength and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1α4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a PGC-1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials.

            Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin-receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia.
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              Efficacy of Exercise Therapy on Cardiorespiratory Fitness in Patients With Cancer: A Systematic Review and Meta-Analysis

              Purpose To evaluate the effects of exercise therapy on cardiorespiratory fitness (CRF) in randomized controlled trials (RCTs) among patients with adult-onset cancer. Secondary objectives were to evaluate treatment effect modifiers, safety, and fidelity. Methods A systematic search of PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library was conducted to identify RCTs that compared exercise therapy to a nonexercise control group. The primary end point was change in CRF as evaluated by peak oxygen consumption (VO 2peak ; in mL O 2 × kg −1 × min −1 ) from baseline to postintervention. Subgroup analyses evaluated whether treatment effects differed as a function of exercise prescription (ie, modality, schedule, length, supervision), study characteristics (ie, intervention timing, primary cancer site), and publication year. Safety was defined as report of any adverse event (AE); fidelity was evaluated by rates of attendance, adherence, and loss to follow-up. Results Forty-eight unique RCTs that represented 3,632 patients (mean standard deviation age, 55 ± 7.5 years; 68% women); 1,990 (55%) and 1,642 (45%) allocated to exercise therapy and control/usual care groups, respectively, were evaluated. Exercise therapy was associated with a significant increase in CRF (+2.80 mL O 2 × kg −1 × min −1 ) compared with no change (+0.02 mL O 2 × kg −1 × min −1 ) in the control group (weighted mean differences, +2.13 mL O 2 × kg −1 × min −1 ; 95% CI, 1.58 to 2.67; I 2 , 20.6; P < .001). No statistical significant differences were observed on the basis of any treatment effect modifiers. Thirty trials (63%) monitored AEs; a total of 44 AEs were reported. The mean standard deviation loss to follow-up, attendance, and adherence rates were 11% ± 13%, 84% ± 12%, and 88% ± 32%, respectively. Conclusion Exercise therapy is an effective adjunctive therapy to improve CRF in patients with cancer. Our findings support the recommendation of exercise therapy for patients with adult-onset cancer.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                TCRM
                tcriskman
                Therapeutics and Clinical Risk Management
                Dove
                1176-6336
                1178-203X
                29 October 2019
                2019
                : 15
                : 1253-1266
                Affiliations
                [1 ]Division of Thoracic Oncology, Shizuoka Cancer Center , Shizuoka, Japan
                Author notes
                Correspondence: Tateaki Naito Division of Thoracic Oncology, Shizuoka Cancer Center , 1007 Shimonagakubo, Nagaizumi, Sunto District, Shizuoka411-0934, JapanTel +81-55-989-5222Fax +81-55-989-5783 Email t.naito@scchr.jp
                Author information
                http://orcid.org/0000-0003-4047-2929
                Article
                196802
                10.2147/TCRM.S196802
                6825473
                31754304
                f80c5453-5967-4e78-a318-856d19a5996e
                © 2019 Naito.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 29 August 2019
                : 08 October 2019
                Page count
                Figures: 1, Tables: 3, References: 95, Pages: 14
                Categories
                Review

                Medicine
                cancer cachexia,physical function,anamorelin,multimodal intervention
                Medicine
                cancer cachexia, physical function, anamorelin, multimodal intervention

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