The design and implementation of caloric restriction for oncology research (CaReFOR): Is starving cancer cells in the clinical realm feasible?

Abstract

Metabolic alterations are now known to underly cancer growth and progression and therapeutic options are being designed to target dysregulation of metabolism. Using dietary alterations in the treatment of cancer, would be an idea way to intervene in a non-toxic manner. While nutritional interventions have been previously used in the setting of cancer prevention and survivorship, we propose using diet as a cancer therapeutic. Preclinical data demonstrate that caloric restriction (CR) augments radiation therapy by decreasing growth of tumor cells and increasing overall survival. We have therefore designed and implemented a clinical trial to determine if caloric restriction could be tolerated in the clinic during cancer therapy. The CaRe FOR Study: A Pilot Trial Evaluating Caloric Restriction for Oncology Research in Early Stage Breast Cancer Patients. Patients with early stage breast cancer, who require breast radiation have been enrolled. The patients undergo a 10 week CR program, during which they reduce their baseline calories by 25% for 2 weeks pre-radiation, 6 weeks during radiation, and 2 weeks post-treatment. The primary endpoint is to determine if breast cancer patients can adhere to CR during radiation therapy. After enrolling, patients log their baseline caloric intake in an online food diary for one week and a calorie target is established by the provider by calculating a 25% reduction. Patients begin dietary alterations after they receive personalized dietary counseling and behavioral modification lessons adapted from the Diabetes Prevention Program, which both continue through the 10 week program. Secondary parameters will determine if an objective measure can be used to monitor patient adherence in the future and include weight and body composition measures, serum biomarkers, quality of life parameters and treatment toxicity. Here, the steps involved in trying to design a successful clinical trial using CR concurrently with standard cancer treatment such as radiation will be outlined. The long-term goal of the study is to be able to guide methods by which dietary interventions can be successfully implemented for all cancer patients and and to demonstrate that CR is a viable treatment option.. This commentary will provide insight into methods to design clinical trials using dietary alterations.