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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

机译:短期禁食对HER2阴性乳腺癌患者对(新)辅助化疗耐受的影响:一项随机试验研究

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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
机译:背景临床前证据表明,短期禁食(STF)保护健康细胞免受化学疗法的副作用,并使癌细胞更容易受到化学疗法的伤害。这项初步研究检查了STF的可行性及其对早期乳腺癌(BC)均一的患者组的化疗耐受性的影响。方法符合条件的患者患有HER2阴性的II / III BC期。接受(新)辅助TAC(多西他赛/阿霉素/环磷酰胺)的妇女在开始化疗之前和之后随机分组禁食24小时,或者根据健康营养的指导原则进食。比较两组的毒性。通过流式细胞仪分析的γ-H2AX水平,量化外周血单个核细胞(PBMC)中化学疗法诱导的DNA损伤。结果纳入13例患者,其中7例随机分配至STF组。 STF的耐受性良好。在STF组中,化疗后7天的平均红细胞和血小板计数显着更高(分别为P?=?0.007、95?%CI 0.106-0.638和P?=?0.00007、95?%CI 38.7-104)。与非STF组相比。两组之间的非血液学毒性无差异。非STF患者CD45?+?CD3-细胞化疗后30min,γ-H2AX水平显着升高,但非STF患者未升高。结论HER2阴性BC患者化疗期间STF耐受良好,降低了TAC的血液毒性。而且,STF可减少化疗后PBMC中的瞬时增加和/或诱导DNA损伤中DNA损伤的更快恢复。需要进行更大的研究来研究更长的禁食期,以更深入地了解STF在化疗期间的可能益处。试验注册ClinicalTrials.gov:NCT01304251,2011年3月

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