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

Abstract

Breast Cancer Research Group (BOOG) 16, * 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.

Fasting-mimicking diet plus chemotherapy in breast cancer treatment

“…Unfortunately, the study was prematurely interrupted because a pre-planned interim analysis showed a lower-than-anticipated pCR rate in the study population, as well as poor patient adherence to the proposed FMD regimen 1 . In addition, the FMD did not provide evident clinical advantages, neither in terms of reduction of AEs (the primary endpoint of the phase II trial) nor in terms of increased pCR rates (the primary endpoint of the phase III trial) 1 . Of note, triple-negative breast cancer (TNBC) patients, who are much more likely to undergo pCR during preoperative ChT 6 , were significantly more represented in the FMD arm than in the control arm (21.5% vs. 10.9%).…”

“…The main cause of lack of adherence to the experimental diet was dislike of specific components of the FMD, which consisted of a plant-based, standardized kit providing~1200 kcal on day 1 and~200 kcal on days 2-4 1 . Alternative FMD regimens, including schemes containing fresh foods, could be associated with better patient compliance, thus potentially resulting in higher antitumor activity 10 .…”

Dieta cetogénica en cáncer: revisión de la literatura

“…La evidencia reportada está basada en diseños de estudios de baja evidencia científica: reportes y series de casos, estudios observacionales y pocos estudios clínicos. El tamaño de la muestra es pequeño en la mayoría de los casos, desde 1 persona hasta 129 pacientes, y con diferentes objetivos en la implementación de la DC (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) . Un punto a resaltar es la dificultad de la adherencia a la dieta, así como los periodos de seguimiento.…”

“…En los tres casos no reportan efectos adversos. La evidencia más basta surge de tres estudios clínicos realizados en glioblastoma, tumores ginecológicos y cáncer de mama (31,38,39) . De estos, 17 de 20 pacientes con glioblastoma accedieron a realizar la DC entre 6 y 8 semanas.…”

“…Los resultados indican que los pacientes con la dieta tipo DIEA no presentaron diferencias en toxicidad a la QT, pese a que en este grupo no se utilizó tratamiento paralelo con glucocorticoides. Además de esto presentaron mayor tolerancia a la RT, acompañado del aumento de los cuerpos cetónicos, disminución de los niveles de glucosa, IGF-1 e insulina (39) .…”