Fast-Mimicking Diet Is Potentially Beneficial for Patients With Solid Tumors

Claudio Vernieri, MD, PhD

Fast-mimicking dieting (FMD) was found to be safe, feasible, and potentially beneficial for patients with various solid tumor types and who were receiving different anticancer therapies, according to a study published in Cancer Discovery. The diet, which involved short-term, severe caloric restriction was associated with a decrease in blood glucose and growth factor concentration, as well as a reduction in peripheral blood immunosuppressive cells, and enhanced intratumor T-cell infiltration, among this population.

Among 99 evaluable participants, the median plasma glucose concentration reduction was 18.6%, the serum insulin reduction was 50.7%, and the serum IGF-1 reduction was 30.3%. Throughout the 8 consecutive cycles, these results remained consistent.

“Our results from a first-in-human clinical trial showed that a scheme of severe short-term calorie restriction was safe and biologically active in patients, and that its activity likely involved the activation of immune responses,” said co-author Claudio Vernieri, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori and the director of the Metabolic Reprogramming in Solid Tumors program at the FIRC Institute of Molecular Oncology, in Milan, Italy, in a press release. “Since calorie restriction is a safe, inexpensive, and potentially effective approach that could be easily combined with standard antineoplastic therapies, we think these findings might have relevant implications for cancer therapy.”

The study assessed a total of 101 patients. These participants had a variety of tumor types and were receiving various standard anticancer therapies. The global compliance rate among these participants was 91.8%; compliance in this case was defined as observing all 8 FMD cycles.

The most common adverse event (AE) associated with the dieting technique was fatigue and was rarely severe (12.9%). Thus, the trial met its primary safety end point.

The diet itself involved the following cycle: 5-days of low-carbohydrate, low-protein, plant derived dieting amounting to a total of 1800 calories (600 calories on day 1 and 300 calories on the subsequent 4 days). This cycle was followed by a period or regular eating for about 3 to 4 weeks and followed by another cycle. The study period involved 8 total cycles. When patients were not observing the FMD cycle, they were not restricted to any dietary regulations, but were encouraged to adhere to a healthy diet and lifestyle.

The loss of body weight that occurred during the 5 days of severe calorie restriction was reversible in most of the patients during the refeeding period.

“This is an especially important finding, because it excludes the risk that patients might undergo progressive weight loss and/or malnourishment, which are associated with reduced efficacy of anticancer therapies and reduced survival,” added Filippo de Braud, MD, director of the Oncology and Hematology Department of Fondazione IRCCS Istituto Nazionale dei Tumori and professor of medical oncology at the University of Milan in Milan, Italy.

Researchers determined that at the conclusion of the 5-day restricted calorie diet, patients had a significant decrease in circulating immunosuppressive myeloid subpopulations and an increase of activated CD8+ T cells. Notably, the various concomitant antitumor therapies did not impact these results. Additionally, a group of cancer-free volunteers also produced the same effects.

To corroborate the findings, researchers also performed an interim analysis of another ongoing trial (DigesT; NCT03454282). Patients in this trial were asked to complete a 5-day FMD cycle 7 to 10 days before undergoing surgery for early-stage breast cancer or melanoma. The tumor-infiltrating immune cells and transcriptomic immune profiles revealed a significant increase in tumor-infiltrating CD8+ T cells and other changes, suggesting that FMD induces an antitumor immune microenvironment.

The study authors concluded that the experimental diet generated favorable immunomodulatory effects at both the systematic and the tumor level. These findings indicate that a coherent immune response originates in the blood and consequently propagates to the tumor.

The main study limitations are related to the heterogeneous nature of the participants; because the patients all had different tumor type and concomitant anticancer therapies, researchers could not conclude the antitumor efficacy of the caloric restriction.

Consequently, the authors have helped to launch a series of new clinical trials, including the BREAKFAST trial (NCT04248998), which will seek to better understand the antitumor effects of the FMD diet among patients with solid tumors. Researchers hope to uncover ways in which diet and caloric restrictions may improve the potency of antineoplastic therapies and potentially prolong the life expectancy of patients in this population.

Reference

Fasting-mimicking diet is safe, may modulate metabolism and boost antitumor immunity in cancer patients. American Association for Cancer Research. News release. November 17, 2021. Accessed November 29, 2021. https://bit.ly/3ELIaZS