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

Abstract

Background: Short-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.

Methods: 3 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.

Results: The 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.

Conclusion: Fasting 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 registration: NCT00936364 , registered propectively on July 9, 2009.

Keywords: Chemotherapy; Fasting; Insulin-like growth factor; Neutropenia; Oxidative stress.

Figures

Fig. 1

Schema of the trial design; cohorts and strategy for escalating fasting duration. R24r signifies 24 hours of fasting without planned food, only rescue. R48r is 48 hours of fasting prior to chemotherapy, without planned food, only rescue. If safety or feasibility failed in the cohort of 48 hours fasting, we planned a “de-escalation” to a 48 hour fasting period with planned rescue food: R48p. However, if 48 hours fasting was safe and feasible, we would escalate to 72 hours fasting, broken down as 48 hours before chemotherapy and 24 hours after, R48/24r

Fig. 2

DNA damage in host cells was measured using peripheral blood mononuclear cells from study subjects using the COMET assay

Fig. 3

Olive moments, indicating DNA damage in peripheral blood mononuclear cells, are shown here by cohort, comparing the chemotherapy-free baseline (BL) to a sample taken after fasting, but before chemotherapy (C1D1 = cycle 1, day 1) and 24 hours after chemotherapy (C1D2 = cycle 1, day 2) and again after fasting but before chemotherapy (C2D1 = cycle 2, day 1). The difference comparing the 48 + 72 hour cohorts to the 24 hour cohort is p=0.08 by F test with ANOVA