Safety and feasibility of fasting in combination with platinum-based chemotherapy.
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.
USC Keck School of Medicine, Norris Comprehensive Cancer Center, 1441 Eastlake Ave. #3440, Los Angeles, CA, 90033, USA.
Tanya B
TB
Dorff
Department of Preventive Medicine, USC Keck School of Medicine, 1441 Eastlake Ave, #4427, Los Angeles, 90033, CA, United States.
Susan
S
Groshen
USC Keck School of Medicine, Norris Comprehensive Cancer Center, 1441 Eastlake Ave. #3440, Los Angeles, CA, 90033, USA.
Agustin
A
Garcia
USC Keck School of Medicine, Norris Comprehensive Cancer Center, 1441 Eastlake Ave. #3440, Los Angeles, CA, 90033, USA.
Manali
M
Shah
Department of Preventive Medicine, USC Keck School of Medicine, 1441 Eastlake Ave, #4427, Los Angeles, 90033, CA, United States.
Denice
D
Tsao-Wei
USC Keck School of Medicine, Department of Obstetrics and Gynecology, 1441 Eastlake Ave, #3440, Los Angeles, 90033, CA, United States.
Huyen
H
Pham
Longevity Institute, University of Southern California Davis School of Gerontology, Department of Biological Sciences, 3715 McClintock Avenue, Los Angeles, 90089, CA, United States.
Chia-Wei
CW
Cheng
Longevity Institute, University of Southern California Davis School of Gerontology, Department of Biological Sciences, 3715 McClintock Avenue, Los Angeles, 90089, CA, United States.
Sebastian
S
Brandhorst
Longevity Institute, University of Southern California Davis School of Gerontology, Department of Biological Sciences, 3715 McClintock Avenue, Los Angeles, 90089, CA, United States.
Pinchas
P
Cohen
Longevity Institute, University of Southern California Davis School of Gerontology, Department of Biological Sciences, 3715 McClintock Avenue, Los Angeles, 90089, CA, United States.
Min
M
Wei
Longevity Institute, University of Southern California Davis School of Gerontology, Department of Biological Sciences, 3715 McClintock Avenue, Los Angeles, 90089, CA, United States. vlongo@usc.edu.
Valter
V
Longo
USC Keck School of Medicine, Norris Comprehensive Cancer Center, 1441 Eastlake Ave. #3440, Los Angeles, CA, 90033, USA. diquinn@usc.edu.
David I
DI
Quinn
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005215:Fasting / Q000097:blood*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D018384:Oxidative Stress; D010984:Platinum / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
D015415:Biomarkers; C583557:IGF1 protein, human; D010984:Platinum; D007334:Insulin-Like Growth Factor I
Chemotherapy; Fasting; Insulin-like growth factor; Neutropenia; Oxidative stress