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

• Published in: BMC cancer Vol. 16; no. 1; p. 360
• Main Authors: Dorff, Tanya B., Groshen, Susan, Garcia, Agustin, Shah, Manali, Tsao-Wei, Denice, Pham, Huyen, Cheng, Chia-Wei, Brandhorst, Sebastian, Cohen, Pinchas, Wei, Min, Longo, Valter, Quinn, David I.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.06.2016; BioMed Central
• Subjects: Adult; Aged; Biomarkers; Biomarkers - blood; Biomarkers - metabolism; Cancer; Cancer patients; Cancer therapies; Chemotherapy; Clinical trials; Consent; Data analysis; Fasting; Fasting - blood; Feasibility Studies; Female; Food; Gene expression; Health aspects; Humans; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Male; Middle Aged; Neoplasms - blood; Neoplasms - drug therapy; Oxidative Stress; Platinum - adverse effects; Platinum - therapeutic use; Safety and security measures; Studies; Treatment Outcome; Tumors; Oxidative stress; Chemotherapy; Fasting; Insulin-like growth factor; Neutropenia
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-016-2370-6

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. 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. 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. 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. NCT00936364 , registered propectively on July 9, 2009.