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. Trial registration germanctr.de: DRKS00011610, registered 30 January, 2017.

BackgroundMetastasis is the leading cause of mortality in malignant diseases. Patients with metastasis often show reduced Lysophosphatidylcholine (LysoPC) plasma levels and treatment of metastatic tumour cells with saturated LysoPC species reduced their metastatic potential in vivo in mouse experiments. To provide a first insight into the interplay of tumour cells and LysoPC, the interactions of ten solid epithelial tumour cell lines and six leukaemic cell lines with saturated and mono-unsaturated LysoPC species were explored.MethodsLysoPC metabolism by the different tumour cells was investigated by a combination of cell culture assays, GC and MS techniques. Functional consequences of changed membrane properties were followed microscopically by detecting lateral lipid diffusion or cellular migration. Experimental metastasis studies in mice were performed after pretreatment of B16.F10 melanoma cells with LysoPC and FFA, respectively.ResultsIn contrast to the leukaemic cells, all solid tumour cells show a very fast extracellular degradation of the LysoPC species to free fatty acids (FFA) and glycerophosphocholine. We provide evidence that the formerly LysoPC bound FFA were rapidly incorporated into the cellular phospholipids, thereby changing the FA-compositions accordingly. A massive increase of the neutral lipid amount was observed, inducing the formation of lipid droplets. Saturated LysoPC and to a lesser extent also mono-unsaturated LysoPC increased the cell membrane rigidity, which is assumed to alter cellular functions involved in metastasis. According to that, saturated and mono-unsaturated LysoPC as well as the respective FFA reduced the metastatic potential of B16.F10 cells in mice. Application of high doses of liposomes mainly consisting of saturated PC was shown to be a suitable way to strongly increase the plasma level of saturated LysoPC in mice.ConclusionThese data show that solid tumours display a high activity to hydrolyse LysoPC followed by a very rapid uptake of the resulting FFA; a mechanistic model is provided. In contrast to the physiological mix of LysoPC species, saturated and mono-unsaturated LysoPC alone apparently attenuate the metastatic activity of tumours and the artificial increase of saturated and mono-unsaturated LysoPC in plasma appears as novel therapeutic approach to interfere with metastasis.

No single AOX, either in plasma or BMC (α-tocopherol, ascorbic acid and ß-carotene), revealed predictive value for the incidence or severity of OM. However, patients with an overall good plasma AOX status tended to require less PN, a common clinical marker for OM, which may be more relevant than any one AOX at reducing the risk of OM.

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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 the fasting-related discomfort and increases the compliance. Methods In this randomised controlled cross-over trial, gynaecologic cancer patients receiving chemotherapy with a minimum of 4 cycles were randomised to mSTF for 96 h during half of chemotherapy cycles and to consume 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 the hunger-suppression effect of a KD. Chemotherapy-induced toxicities, fasting-related discomfort, body composition, quality of life, laboratory values, and compliance were assessed on each chemotherapy. Results Thirty patients (30-74 years) completed the study. During mSTF frequency and severity scores 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 score of total toxicities were significantly reduced [-10.36 ± 4.44; 95% CI -19.22 - (-1.50); P = 0.023]. Additionally, significant fewer postponements of the chemotherapy were observed post-mSTF, reflecting an improved tolerance of chemotherapy [-0.80 ± 0.37; 95% CI -1.53 – (-0.06); P = 0.034]. A significant reduction of mean body weight by -0.79 ± 1.47 kg during mSTF could not be compensated and remained until the end of study ( 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] significantly decreased during fasting. The KD as fasting supportive diet could neither reduce fasting-related discomfort nor increase compliance of our fasting regime. Conclusion MSTF is safe and feasible in gynaecologic cancer patients. The results indicate that mSTF during chemotherapy can reduce chemotherapy-induced toxicities and increase the tolerance of chemotherapy. Larger clinical trials are required to recommend mSTF for cancer patients.