Brief Quasi-Fasting Diet Boosts Breast Cancer Chemo Response

A fasting mimicking diet (FMD) – a low-calorie, low-protein, plant-based, intermittent meal plan with the metabolic benefits of fasting -- used over several days was a safe and effective adjunct to chemotherapy in women with early breast cancer, a randomized trial showed.

FMD significantly boosted the effects of neoadjuvant chemotherapy on the radiological and pathological tumor response in women with HER2-negative stage 2/3 breast cancer.

Results from the DIRECT trial, led by Stefanie de Groot, MD, of Leiden University Medical Center in the Netherlands, was published in Nature Communications.

"We've been talking about intermittent fasting for a long time, so this isn't out of the blue," said Virginia Kaklamani, MD, of the Mays Cancer Center at UT Health San Antonio.

"The concept is based on a lot of preclinical data that we have, and not just with chemotherapy," Kaklamani, who was not involved in the study, told MedPage Today. "When you look at how the body's metabolism changes by intermittent fasting, it's pretty fascinating because you decrease a lot of the inflammatory markers, you decrease a lot of growth factors like insulin. And so the thought is that it could be a good anti-cancer therapy by itself."

According to de Groot and colleagues, healthy cells will switch from a proliferative state to a maintenance and repair state with fasting, while malignant cells don't adapt to a nutrient scarce environment. "Instead, fasting deprives proliferating cancer cells of nutrients, growth and other factors, which renders them more sensitive to cancer therapy and increases cell death," they explained.

In the multicenter, open label, phase II study, with enrollment from February 2014 to January 2018, 129 patients with early breast cancer were randomized to either FMD as an adjunct to chemotherapy, or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. These patients were without diabetes and had BMI values over 18.

"The FMD is a 4-day plant-based low amino-acid substitution diet, consisting of soups, broths, liquids and tea," the researchers explained. Daily energy value was about 1,200 kcal on day 1 but was reduced to approximately 200 kcal/day over days 2-4, which constituted the intervention period. During those 3 days, complex carbohydrates accounted for about 80% of the calorie count.

Thirty of the patients received six cycles of so-called FEC-T chemotherapy (5-fluorouracil, epirubicin, cyclophosphamide, and docetaxel), while the remaining 99 received eight cycles of AC-T (doxorubicin, cyclophosphamide, docetaxel). Control patients but not the FMD group also received dexamethasone pretreatment to minimize nausea and vomiting.

Of the 65 patients randomized to receive the FMD, 81.5% completed the first FMD cycle, more than 50% completed two cycles, and 20% complied with the FMD diet during all cycles of chemotherapy.

Intention to treat analysis revealed an overall pathologic complete response rate of 11.7%, with no significant difference between the two groups (10.8% in FMD group versus 12.7% in control group; OR 0.830, 95% CI 0.282–2.442). However, radiologically complete or partial responses occurred about three times more often in the FMD group compared to the control group in both univariate (OR 2.886, 95% CI 1.012-8.227) and multivariate (OR 3.168, 95% CI 1.062-9.446) analyses. Thus, the number of patients who had stable or progressive disease was markedly lower in the FMD group (11.3%) than in the control group (26.9%).

A per-protocol analysis was performed comparing patients who were compliant with the FMD for at least half of the cycles with less compliant FMD patients and with the control group. Miller and Payne pathological response of 4/5 (representing 90%-100% tumor cell loss) occurred more often in FMD patients than in the control group in both univariate (OR 3.194, 95% CI 1.115–9.152) and multivariate analyses (OR 4.109, 95% CI 1.297–13.02).

There was no significant difference in toxicity between the two groups even though patients in the FMD group did not take dexamethasone. "This suggests that the FMD may obviate the need for dexamethasone in the prevention of the side effects of chemotherapy," wrote de Groot and her colleagues.

"The study was well conducted," said Kaklamani. "It didn't have tons of patients but it still had a good number and the results were significant. I think we need larger studies, and the issue is always going to be compliance, but for people who can do this diet, I think this could benefit them."

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