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The findings indicated that a fasting mimicking diet is safe and effective as an adjunct to chemotherapy in women with early breast cancer.
Study results from the phase 2 DIRECT study are the first to indicate that a fasting mimicking diet (FMD) is safe and effective as an adjunct to chemotherapy in women with early breast cancer.1
The findings, published in Nature Communications, build upon preclinical evidence suggesting that fasting and FMDs prior to chemotherapymay have a beneficial effect on both the efficacy of a wide variety of cancer therapies and on the reduction of the side effects caused by various cancer treatments.
"This revelatory study on the benefits of a plant-based, Fasting Mimicking Diet during chemotherapy may represent a major breakthrough for women undergoing breast cancer treatments," breast surgeon Kristi Funk, MD, former director of the Breast Center at Cedars-Sinai Medical Center, said in a press release.2 "This study supports the concept that FMD creates the metabolic environment that supports chemo's ability to destroy cancer cells while minimizing the collateral damage to normal cells. With an FMD, you get to eat, so you're not too hangry, but your cells still respond as if you're strictly fasting.”
The multicenter, open-label, randomized, phase 2 trial evaluated 129 patients with HER2-negative stage II/III breast cancer, 65 of which received FMD as an adjunct to chemotherapy and 64 of which used their regular diet. Notably, 30 patients received FEC-T chemotherapy and 99 received AC-T.
Of the 65 patients who received FMD, 53 (81.5%) completed the first FMD cycle, over 50% completed 2 FMD cycles, 33.8% used the FMD for at least 4 cycles (all AC or FEC cycles), and 20.0% of the patients complied during all cycles of chemotherapy. In the regular diet group, 5 (7.8%) patients were not compliant and decided to fast during one or more cycles of chemotherapy.
“The main reason for non-adherence to the FMD was dislike of distinct components of the diet, perhaps induced by chemotherapy,” the study authors wrote.
The overall pCR rate was 11.7% and did not differ between the 2 groups (10.8% in FMD group versus 12.7% in control group; OR, 0.830; 95% CI, 0.282-2.442; P = 0.735). The radiologically complete or partial response, as measured by MRI or ultrasound before surgery, occurred approximately 3 times more often in the FMD group compared to the control group in univariate (OR, 2.886; 95% CI, 1.012-8.227; P = 0.047) and multivariate (OR, 3.168; 95% CI, 1.062-9.446; P = 0.039) analyses. Similarly, the proportion of patients with stable or progressive disease was 2.5-fold lower in the FMD group (11.3%) than in the control group (26.9%).
In the per protocol analysis, the pCR rate did not differ between the compliant FMD patients (13.6%) and controls (12.1%; OR, 1.150; 95% CI, 0.269-4.911; P = 0.850). However, the Miller and Payne pathological response 4/5 (90–100% tumor cell loss) occurred more often in patients using FMD in both univariate (OR, 3.194; 95% CI, 1.115-9.152; P = 0.031) and multivariate analyses (OR, 4.109; 95% CI, 1.297-13.02; P = 0.016). Even further, the more FMD cycles completed, the more patients had either a complete or partial radiological response to therapy (P for trend = 0.035). Both analyses were adjusted for hormone receptor status, TNM stage, BMI, and chemotherapy regimen.
Grade 3-4 toxicity, scored across all cycles of chemotherapy, was not found to be significantly different between the FMD group (75.4%) and the regular diet group (65.6%), and no grade 5 toxicities occurred. Moreover, the percentage of patients who discontinued chemotherapy did not significantly differ between either group (27.7% FMD vs 23.8% control; P = 0.580). Importantly though, while side effects were similar in both arms, patients in the FMD arm did not receive dexamethasone before the AC chemotherapy cycles.
"This research essentially found that fasting switches healthy cells from a busy, proliferative state to a quiet, maintenance mode. Why? There's low level of nutrient and insulin around, so it's time to conserve energy. Malignant cells, however, don't listen to these body's signals and don't respond to food scarcity by entering this protective mode,” Funk explained. “Because chemo targets cells that divide quickly, when you receive it in a fasted state, it should sail past quiet healthy cells and more effectively target the busy cancer cells.”
The investigators indicated that this data should be cautiously interpreted though, especially those of the per protocol analysis due to the risk of selection bias.
“These findings together with preclinical data encourage further exploration of the benefits of fasting/FMD in patients receiving a wide range of cancer therapies,” the authors wrote.
1. de Groote S, Lugtenberg RT, Cohen D, et al. Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nature Communications. doi: 10.1038/s41467-020-16138-3.
2. New Peer-Reviewed Research Shows Fasting Mimicking Diets May Enhance Effectiveness of Chemotherapy in Cancer Patients, While Reducing Some Side Effects [news release]. Los Angeles, CA. Published June 25, 2020. prnewswire.com/news-releases/new-peer-reviewed-research-shows-fasting-mimicking-diets-may-enhance-effectiveness-of-chemotherapy-in-cancer-patients-while-reducing-some-side-effects-301083930.html. Accessed July 15, 2020.