Abstract 4417: Fasting protects against the adverse side effects of chemotherapy but has no effect on antitumor activity.
Authors: Huisman Sander A. , van den Engel Sandra , Roest Henk P. , IJzermans Jan N.M. , de Bruin Ron W.F. 
Published: August 2014

Abstract
The multi-modality approach to colorectal liver metastases has led to an increase in the number of patients eligible for hepatic resection. The tumor response to chemotherapeutic drugs plays a pivotal role in the success of this approach. The limitations to their use are often severe adverse side-effects, resulting in an early discontinuation of the chemotherapy. In previous work we have shown that fasting leads to increased expression of cytoprotective and antioxidant genes. In this study we have examined the effects of fasting prior to administration of a high dose of the chemotherapeutic agent irinotecan on the occurrence of chemotherapy-associated adverse events and anti-tumor effect in C26 coloncarcinoma bearing mice.
Male BALB/c mice were subcutaneously implanted with a 15 mm3 cube of C26 coloncarcinoma cells and divided into 4 groups (n=6/group). Ten days after implantation, 2 groups were fasted for 72 hours and 2 groups were fed ad libitum. After 72 hours all groups were fed ad libitum again. One ad libitum group and one fasting group were treated with a cumulative dose of 400 mg/kg irinotecan ip, administered on days 0, 2 and 4 relative to fasting. Tumor growth was measured daily using Vernier calipers. Ocurrence of adverse side effects was recorded daily. Leucocytes were counted on day 8 after the first irinotecan dose. All mice were sacrificed 10 days after the first irinotecan injection or earlier when tumor volume exceeded allowable range. Tumors were resected, measured and weighted.
In the ad libitum fed group mice showed weight loss from the first irinotecan injection, while the fasted mice gained weight during the observation period. In the ad libitum fed mice other adverse side effects were observed from day 4 after the first irinotecan gift. They displayed different behaviour, reduced mobility, had ruffled hair, a hunched posture and diarrhea. The fasted mice showed no visible adverse side effects. The number of leukocytes in the fasted group treated with irinotecan was significantly higher, than in the ad libitum fed treated animals (6.5*10ˆ6/mL vs. 3.2*10ˆ6/mL, p&lt;0.001). The experiment had to be terminated before the end of the observation period in 67% of the non-treated mice due to progressive tumor growth. In both irinotecan treated groups tumor growth was similarly suppressed compared with the fasted and ad libitum fed groups without irinotecan (1271 mg vs. 2106 mg, p&lt;0.001).
Our data demonstrate that 72 hours of fasting prior to treatment with a high dose of irinotecan prevents the occurrence of adverse side effects, while the antitumor activity is not affected. These data suggest that a preoperative fasting regimen may improve the therapeutic index of chemotherapeutic agents and increases the efficacy of chemotherapeutic treatment.
Citation Format: Sander A. Huisman, Sandra van den Engel, Henk P. Roest, Jan N.M. IJzermans, Ron W.F. de Bruin. Fasting protects against the adverse side effects of chemotherapy but has no effect on antitumor activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4417. doi:10.1158/1538-7445.AM2013-4417