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      Chemotherapy and Targeted Agents in the Treatment of Elderly Patients with Metastatic Colorectal Cancer

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          Abstract

          Colorectal cancer (CRC) is one of the main causes of cancer death in the elderly. The older patients constitute a heterogeneous group in terms of functional status, comorbidities, and aging-related conditions. Therefore, therapeutic decisions need to be individualized. Additionally, a higher toxicity risk comes from the fact that pharmacokinetics and pharmacodynamics of the drugs as well as the tissue tolerance can be altered with aging. Although the chemotherapy efficacy in metastatic colorectal cancer (mCRC) is similar for older and young patients, more toxicity is presented in the elderly. While the mono-chemotherapy provides the same benefit for young and older patients, doublets front-line chemotherapy improves progression-free survival (PFS) but not overall survival (OS) in the elderly. Furthermore, the benefit of the addition of bevacizumab to chemotherapy in older patients has been shown in several clinical trials, while the clinical data for the benefit of anti-epidermal growth factor antibodies are scarcer. Immunocheckpoint inhibitors could be an appropriate option for patients with microsatellite instability (MSI) tumors. A prior geriatric assessment is required before deciding the type of treatment in order to offer the best therapeutic option.

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          Frailty in Older Adults: Evidence for a Phenotype

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            Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study

            Metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer has a poor prognosis after treatment with conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-infiltrating lymphocytes, and checkpoint regulators. All of these features are associated with the response to PD-1 blockade in other tumour types. Therefore, we aimed to study nivolumab, a PD-1 immune checkpoint inhibitor, in patients with dMMR/MSI-H metastatic colorectal cancer.
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              Frailty consensus: a call to action.

              Frailty is a clinical state in which there is an increase in an individual's vulnerability for developing increased dependency and/or mortality when exposed to a stressor. Frailty can occur as the result of a range of diseases and medical conditions. A consensus group consisting of delegates from 6 major international, European, and US societies created 4 major consensus points on a specific form of frailty: physical frailty. 1. Physical frailty is an important medical syndrome. The group defined physical frailty as "a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual's vulnerability for developing increased dependency and/or death." 2. Physical frailty can potentially be prevented or treated with specific modalities, such as exercise, protein-calorie supplementation, vitamin D, and reduction of polypharmacy. 3. Simple, rapid screening tests have been developed and validated, such as the simple FRAIL scale, to allow physicians to objectively recognize frail persons. 4. For the purposes of optimally managing individuals with physical frailty, all persons older than 70 years and all individuals with significant weight loss (>5%) due to chronic disease should be screened for frailty. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                11 December 2020
                December 2020
                : 9
                : 12
                : 4015
                Affiliations
                [1 ]Department of Medical Oncology, Hospital Clinic, 08036 Barcelona, Spain; atuca@ 123456clinic.cat
                [2 ]Department of Medical Oncology, General Hospital of Granollers, 08402 Granollers, Spain; rosagallegosanchez@ 123456gmail.com
                [3 ]Department of Medical Oncology, Hospital Universitario La Paz, CIBERONC, 28046 Madrid, Spain; isma_g_c@ 123456hotmail.com
                [4 ]Department of Medical Oncology, University General Hospital of Valencia, CIBERONC, 46014 Valencia, Spain; mir_gil@ 123456hotmail.com
                [5 ]Cátedra UAM-AMGEN, 28049 Madrid, Spain
                Author notes
                Author information
                https://orcid.org/0000-0002-4633-5856
                https://orcid.org/0000-0002-4508-7395
                Article
                jcm-09-04015
                10.3390/jcm9124015
                7764481
                33322567
                c6324aaf-6c91-4a1b-a443-982e3970a78b
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 November 2020
                : 07 December 2020
                Categories
                Review

                metastatic colorectal cancer,elderly,chemotherapy,targeted therapies,geriatric assessment

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