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短期禁食对HER2阴性乳腺癌患者新辅助化疗耐受性的影响:一项随机对照试验研究

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

作者信息

de Groot Stefanie, Vreeswijk Maaike P G, Welters Marij J P, Gravesteijn Gido, Boei Jan J W A, Jochems Anouk, Houtsma Daniel, Putter Hein, van der Hoeven Jacobus J M, Nortier Johan W R, Pijl Hanno, Kroep Judith R

机构信息

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.

出版信息

BMC Cancer. 2015 Oct 5;15:652. doi: 10.1186/s12885-015-1663-5.

DOI:10.1186/s12885-015-1663-5
PMID:26438237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4595051/
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.

摘要

背景

临床前证据表明,短期禁食(STF)可保护健康细胞免受化疗副作用的影响,并使癌细胞更容易受到化疗的作用。这项初步研究探讨了短期禁食在早期乳腺癌(BC)同质患者群体中的可行性及其对化疗耐受性的影响。

方法

符合条件的患者为HER2阴性的II/III期乳腺癌患者。接受(新)辅助TAC(多西他赛/阿霉素/环磷酰胺)治疗的女性被随机分为两组,一组在开始化疗前后禁食24小时,另一组按照健康营养指南进食。比较两组的毒性。通过流式细胞术分析γ-H2AX水平来量化化疗诱导的外周血单核细胞(PBMC)中的DNA损伤。

结果

纳入了13名患者,其中7名被随机分配到短期禁食组。短期禁食耐受性良好。与非短期禁食组相比,短期禁食组化疗后7天的平均红细胞和血小板计数显著更高(分别为P = 0.007,95%CI 0.106 - 0.638和P = 0.00007,95%CI 38.7 - 104)。两组间非血液学毒性无差异。在非短期禁食组中,化疗后30分钟CD45 + CD3-细胞中的γ-H2AX水平显著升高,而短期禁食组患者未出现这种情况。

结论

化疗期间的短期禁食耐受性良好,并降低了HER2阴性乳腺癌患者TAC的血液学毒性。此外,短期禁食可能会减少化疗后PBMC中DNA损伤的短暂增加和/或促进其更快恢复。需要进行更大规模的研究,调查更长的禁食期,以更深入了解化疗期间短期禁食的潜在益处。

试验注册

ClinicalTrials.gov:NCT01304251,2011年3月。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be50/4595051/3303a1b94cda/12885_2015_1663_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be50/4595051/3a3a6a7cdda2/12885_2015_1663_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be50/4595051/3303a1b94cda/12885_2015_1663_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be50/4595051/3a3a6a7cdda2/12885_2015_1663_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be50/4595051/3303a1b94cda/12885_2015_1663_Fig2_HTML.jpg

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