Quality of life and illness perceptions in patients with breast cancer using a fasting mimicking diet as an adjunct to neoadjuvant chemotherapy in the phase 2 DIRECT (BOOG 2013-14) trial.

PURPOSE: In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness perceptions regarding the possible side effects of chemotherapy and the FMD were secondary outcomes of the trial. METHODS: 131 patients with HER2-negative stage II/III breast cancer were recruited, of whom 129 were randomly assigned (1:1) to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and the day of neoadjuvant chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires EORTC-QLQ-C30 and EORTC-QLQ-BR23; the Brief Illness Perception Questionnaire (BIPQ) and the Distress Thermometer were used to assess these outcomes at baseline, halfway chemotherapy, before the last cycle of chemotherapy and 6 months after surgery. RESULTS: Overall QoL and distress scores declined during treatment in both arms and returned to baseline values 6 months after surgery. However, patients' perceptions differed slightly over time. In particular, patients receiving the FMD were less concerned and had better understanding of the possible adverse effects of their treatment in comparison with patients on a regular diet. Per-protocol analyses yielded better emotional, physical, role, cognitive and social functioning scores as well as lower fatigue, nausea and insomnia symptom scores for patients adherent to the FMD in comparison with non-adherent patients and patients on their regular diet. CONCLUSIONS: FMD as an adjunct to neoadjuvant chemotherapy appears to improve certain QoL and illness perception domains in patients with HER2-negative breast cancer. Trialregister ClinicalTrials.gov Identifier: NCT02126449.

Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial.

Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast cancer, without diabetes and a BMI over 18 kg m-2, to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite the fact that dexamethasone was omitted in the FMD group. A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P = 0.039). Moreover, per-protocol analysis reveals that the Miller&Payne 4/5 pathological response, indicating 90-100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P = 0.016). Also, the FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes. These positive findings encourage further exploration of the benefits of fasting/FMD in cancer therapy. Trial number: NCT02126449.