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

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

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.

Figures

Fig. 1
Fig. 1
Metabolic, endocrine and inflammatory parameters on day 0 compared between STF and non-STF subjects. Values are measured on day 0 immediately before chemotherapy infusion (during the use of prophylactic dexamethasone). Mean values of different patients of different cycles (1–6) are combined to test differences between both treatment groups. * P value <0.05. Reference values: glucose 3.1-6.4 mmol/L; insulin 0-20 mU/L; IGF-1 5.4-24.3 nmol/L; IGF-BP3 2.2-5.8 mg/L; TSH 0.3-4.8 mU/L; FT412-22pmol/L, T31.1-3.1 nmol/L; CRP 0.0-5.0 mg/L;. IGF-1; Abbreviations: STF: short-term fasting, IGF-1:Insulin-like growth factor 1, IGF-BP3: insulin- like growth factor binding protein 3, TSH: thyroid-stimulating hormone; FT4:,free thyroxine; T3: CRP; C-reactive protein
Fig. 2
Fig. 2
Hematologic parameters compared between both groups. Values are measured on day 0 of cycle 1 immediately before the chemotherapy infusion, on day 7 of cycle 1–5 combined and day 21 of cycle 1–5 combined. * P value <0.05. STF; short-term fasting, Reference values: erythrocytes 4-5*1012/L; thrombocytes 150-400*109/L

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