Impact of modified short-term fasting and its combination with a fasting supportive diet during chemotherapy on the incidence and severity of chemotherapy-induced toxicities in cancer patients - a controlled cross-over pilot study

Background: This pilot trial aimed to investigate whether modified short-term fasting (mSTF) reduces the incidence of chemotherapy-induced toxicities and whether an initial ketogenic diet (KD) as fasting supportive diet reduces fasting-related discomfort and improves the compliance. Methods: In this controlled cross-over trial, gynaecologic cancer patients undergoing chemotherapy with a minimum of 4 cycles fasted for 96 h during half of their chemotherapy cycles and consumed a normocaloric diet during the other chemotherapy cycles. The caloric intake during mSTF was restricted to 25% of each patient's daily requirement. In addition, half of the patients should eat a 6-day normocaloric KD prior to each mSTF period to investigate a KD's hunger-suppression effect. Chemotherapy-induced toxicities, fasting-related discomfort, body composition, quality of life, laboratory values, and compliance were assessed at each chemotherapy. Results: Thirty patients aged 30-74 years (median 54 years) completed the study. During mSTF the frequency and severity score of stomatitis [- 0.16 +/- 0.06; 95% CI -0.28 - (- 0.03); P = 0.013], headaches [- 1.80 +/- 0.55; 95% CI -2.89 (- 0.71); P = 0.002], weakness [- 1.99 +/- 0.87; 95% CI -3.72 - (- 0.26); P = 0.024] and the total toxicities' score were significantly reduced [- 10.36 +/- 4.44; 95% CI -19.22 - (- 1.50); P = 0.023]. We also observed significantly fewer chemotherapy postponements post-mSTF, reflecting improved tolerance of chemotherapy [- 0.80 +/- 0.37; 95% CI -1.53 - (- 0.06); P = 0.034]. A significant reduction in mean body weight by - 0.79 +/- 1.47 kg during mSTF was not compensated and remained until study's conclusion (P < 0.005). On average, Insulin [- 169.4 +/- 44.1; 95% CI -257.1 (- 81.8); P < 0.001] and Insulin-like growth factor 1 levels [- 33.3 +/- 5.4; 95% CI -44.1 - (- 22.5); P < 0.001] dropped significantly during fasting. The KD as a fasting supportive diet neither reduced fasting-related discomfort nor improved compliance of our fasting regimen. Conclusion: MSTF is safe and feasible in gynaecologic cancer patients. Our results indicate that mSTF during chemotherapy can reduce chemotherapy-induced toxicities and enhance the tolerance of chemotherapy. Larger clinical trials are required to recommend mSTF for cancer patients.