Safety and feasibility of fasting in combination with platinum-based chemotherapy

Abstract

BackgroundShort-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients.Methods3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state.ResultsThe median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period.ConclusionFasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting.Trial registrationNCT00936364, registered propectively on July 9, 2009.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2370-6) contains supplementary material, which is available to authorized users.

Impact of intermittent fasting on health and disease processes

“…Recently a series of studies in animal models have shown that periodic fasting (PF) lasting 2 or more days can be as effective as chemotherapy in delaying the progression of a wide range of cancers but, more importantly, can protect normal cells from the toxic effects of chemotherapy drugs while sensitizing cancer cells to the treatment (Raffaghello et al, 2008; Lee et al, 2012; Safdie et al, 2009; Dorff et al, 2016; Lee and Longo, 2011). A severely restricted diet that mimics PF started at middle age was effective in causing a major reduction in tumor incidence, in addition to delaying tumor onset and reducing the number of sites with tumor-like lesions, suggesting a reduction in metastatic cancers (Brandhorst et al, 2015).…”

Protective effects of short-term dietary restriction in surgical stress and chemotherapy

“…In cases where cancer progression could be monitored, no evidence was found that fasting interferes with chemotherapy efficacy or protects the tumors (Safdie et al, 2009). In a dose-escalation study of 24–72 h of fasting prior to platinum-based chemotherapy in 20 cancer patients, IGF-1 levels decreased and 72 h of fasting was considered safe and feasible (Dorff et al, 2016). The results from a phase I clinical trial indicate that 72 h of PF in combination with chemotherapy were associated with normal lymphocyte counts and maintenance of a normal lineage balance in white blood cells, analogous to the PF effects on the murine immune system (Cheng et al, 2014; Safdie et al, 2009).…”

Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer

“…An important role for ketone body-mediated protection was obtained from the study by Dorff et al [132] in which longer fasting duration prior to chemotherapy appeared more protective, yet only BHB, but not insulin, IGF-1 or glucose, were significantly different between 24 and 48 h of fasting prior to chemotherapy. This supports the hypothesis that KDs might be used as fasting-mimicking diets to reduce side effects from oxidative stress during prolonged treatment situations such as during several weeks of RT.…”

“…All of the preclinical studies summarized in table 1 have confirmed a reduction of side effects from a variety of chemotherapeutic drugs without interfering with, or even boosting, their anti-tumor effects. To date, 3 small studies in humans have also found evidence of a protective effect of STF against chemotherapy-related toxicity [130,131,132]. These studies and their relevance for patients receiving chemotherapy have been discussed in detail elsewhere [133,134,135,136] and will only briefly be reviewed here.…”

“…The intervention group who fasted for 24 h prior up to 24 h after chemotherapy administration experienced a significant reduction in IGF-1 levels and lower insulin levels than the control group and exhibited signs of less DNA damage or more efficient DNA double-strand break repair in peripheral blood mononuclear cells [134]. The third study was a dose escalation study in a heterogeneous sample of 20 cancer patients who underwent 2 cycles of platinum-based chemotherapy in combination with fasting [132]. There was no control group, but the results indicated an inverse dose-response relationship between the fasting duration and the amount of DNA damage in peripheral blood mononuclear cells as well as the chemotherapy-induced myelosuppression [136].…”