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

BMC Cancer. 2016 Jun 10;16:360. doi: 10.1186/s12885-016-2370-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Fasting / blood*
  • Feasibility Studies
  • Female
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Oxidative Stress
  • Platinum / adverse effects*
  • Platinum / therapeutic use
  • Treatment Outcome

Substances

  • Biomarkers
  • IGF1 protein, human
  • Platinum
  • Insulin-Like Growth Factor I

Associated data

  • ClinicalTrials.gov/NCT00936364