Participants: Fasting before chemotherapy; 70 patients [Published Data on 20 patients]
Study: Randomized, Interventional, Parallel Assignment (July 9, 2009 – July 9, 2021)
Location: University of Southern California, Los Angeles, CA; in collaboration with Norris Cancer Center
Researcher: Valter Longo, PhD; Dr. David Quinn (email@example.com); Shahmim Jhimlee (firstname.lastname@example.org)
Published: Dorff, T. B., Groshen, S., Garcia, A., Shah, M., Tsao-Wei, D., Pham, H., … Quinn, D. I. (2016). Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer, 16, 360.
Synopsis: This partially randomized clinical trial studies short-term fasting in reducing side effects in patients receiving gemcitabine hydrochloride and cisplatin for advanced solid tumors. Short-term fasting before chemotherapy may reduce the side effects caused by chemotherapy. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
I. To determine the safety and feasibility of short-term fasting prior to administration of combination chemotherapy with platinum in patients with advanced solid tumor malignancies.
II. To evaluate the toxicity profile of platinum-based chemotherapy in subjects who eat normally compared to those who undertake short-term starvation.
III. To investigate changes in plasma insulin, glucose, IGF1 and IGF binding protein (IGFBP) levels, and oxidative stress markers in subjects who undertake short-term fasting compared to controls.
IV. To investigate whether changes in grp78 expression occur after fasting and after chemotherapy administration in human subjects.
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 ongoing randomized trial is studying the effect of 72 h of fasting.
Trial registration: ClinicalTrials.gov -- NCT00936364