Safety and Feasibility of Fasting-Mimicking Diet and Effects on Nutritional Status and Circulating Metabolic and Inflammatory Factors in Cancer Patients Undergoing Active Treatment

SIMPLE SUMMARY: Our phase I/II clinical trial demonstrated that periodic cycles of a modified fasting regime (“fasting-mimicking diet” (FMD) by L-Nutra) were feasible and safe in cancer patients at low nutritional risk and that they did not negatively affect the patients’ body composition when combined with dietary and muscle training instructions to promote lean body mass re-gain in the periods between FMD cycles. While previously published studies of modified fasting in cancer patients exclusively enrolled patients receiving chemotherapy, in our trial, we also accrued patients treated with different types of therapies, including endocrine therapies (w/ or w/o CDK4/6 inhibitors), TKIs, proteasome inhibitors, immune check point inhibitors and radiotherapy. Eighteen different types of cancer are represented in our trial. Our study also shows that the FMD decreased fat mass and effectively lowered the circulating insulin, IGF1 and leptin. These are important elements of novelty of our study when compared to previously published trials. ABSTRACT: In preclinical studies, fasting was found to potentiate the effects of several anticancer treatments, and early clinical studies indicated that patients may benefit from regimes of modified fasting. However, concerns remain over possible negative impact on the patients’ nutritional status. We assessed the feasibility and safety of a 5-day “Fasting-Mimicking Diet” (FMD) as well as its effects on body composition and circulating growth factors, adipokines and cyto/chemokines in cancer patients. In this single-arm, phase I/II clinical trial, patients with solid or hematologic malignancy, low nutritional risk and undergoing active medical treatment received periodic FMD cycles. The body weight, handgrip strength and body composition were monitored throughout the study. Growth factors, adipokines and cyto/chemokines were assessed by ELISA. Ninety patients were enrolled, and FMD was administered every three weeks/once a month with an average of 6.3 FMD cycles/patient. FMD was largely safe with only mild side effects. The patients’ weight and handgrip remained stable, the phase angle and fat-free mass increased, while the fat mass decreased. FMD reduced the serum c-peptide, IGF1, IGFBP3 and leptin levels, while increasing IGFBP1, and these modifications persisted for weeks beyond the FMD period. Thus, periodic FMD cycles are feasible and can be safely combined with standard antineoplastic treatments in cancer patients at low nutritional risk. The FMD resulted in reduced fat mass, insulin production and circulating IGF1 and leptin. This trial was registered on Clinicaltrials.gov in July 2018 with the identifier NCT03595540.