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      The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study

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          Abstract

          Background

          Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC).

          Methods

          Eligible patients had HER2-negative, stage II/III BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) were randomized to fast 24 h before and after commencing chemotherapy, or to eat according to the guidelines for healthy nutrition. Toxicity in the two groups was compared. Chemotherapy-induced DNA damage in peripheral blood mononuclear cells (PBMCs) was quantified by the level of γ-H2AX analyzed by flow cytometry.

          Results

          Thirteen patients were included of whom seven were randomized to the STF arm. STF was well tolerated. Mean erythrocyte- and thrombocyte counts 7 days post-chemotherapy were significantly higher ( P = 0.007, 95 % CI 0.106-0.638 and P = 0.00007, 95 % CI 38.7-104, respectively) in the STF group compared to the non-STF group. Non-hematological toxicity did not differ between the groups. Levels of γ-H2AX were significantly increased 30 min post-chemotherapy in CD45 + CD3- cells in non-STF, but not in STF patients.

          Conclusions

          STF during chemotherapy was well tolerated and reduced hematological toxicity of TAC in HER2-negative BC patients. Moreover, STF may reduce a transient increase in, and/or induce a faster recovery of DNA damage in PBMCs after chemotherapy. Larger studies, investigating a longer fasting period, are required to generate more insight into the possible benefits of STF during chemotherapy.

          Trial registration

          ClinicalTrials.gov: NCT01304251, March 2011

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12885-015-1663-5) contains supplementary material, which is available to authorized users.

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          Most cited references34

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          Pharmacogenomics--drug disposition, drug targets, and side effects.

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            Genetic links between diet and lifespan: shared mechanisms from yeast to humans.

            Caloric restriction is the only known non-genetic intervention that robustly extends lifespan in mammals. This regimen also attenuates the incidence and progression of many age-dependent pathologies. Understanding the genetic mechanisms that underlie dietary-restriction-induced longevity would therefore have profound implications for future medical treatments aimed at tackling conditions that are associated with the ageing process. Until recently, however, almost nothing was known about these mechanisms in metazoans. Recent advances in our understanding of the genetic bases of energy sensing and lifespan control in yeast, invertebrates and mammals have begun to solve this puzzle. Evidence is mounting that the brain has a crucial role in sensing dietary restriction and promoting longevity in metazoans.
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              Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans.

              Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown. Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg(-1) of body weight per day to 0.95 g kg(-1) of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL(-1) to 152 ng mL(-1). These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.
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                Author and article information

                Contributors
                S.de_Groot2@lumc.nl
                M.P.G.Vreeswijk@lumc.nl
                M.J.P.SchoenmaekersWelters@lumc.nl
                G.Gravesteijn@lumc.nl
                J.J.W.A.Boei@lumc.nl
                A.Jochems@lumc.nl
                D.Houtsma@lumc.nl
                H.Putter@lumc.nl
                J.J.M.van_der_Hoeven@lumc.nl
                J.W.R.Nortier@lumc.nl
                H.Pijl@lumc.nl
                +31715263464 , J.R.Kroep@lumc.nl
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                5 October 2015
                5 October 2015
                2015
                : 15
                : 652
                Affiliations
                [ ]Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC Leiden, The Netherlands
                [ ]Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
                [ ]Department of Internal Medicine, Haga Hospital, The Hague, The Netherlands
                [ ]Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
                [ ]Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
                Article
                1663
                10.1186/s12885-015-1663-5
                4595051
                26438237
                dd0be500-2886-464e-8cc3-57b1cba8b8ed
                © de Groot et al. 2015

                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
                : 4 February 2015
                : 28 September 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Oncology & Radiotherapy
                early stage breast cancer,chemotherapy,short-term fasting,toxicity,dna damage

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