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

Introduction:

Acute side effects are often the reason for the premature discontinuation of and/or dose reduction in chemotherapy (CTX). Currently, nutritional supportive therapies during cancer treatment such as modified short-term fasting are discussed. A wide range of cell and animal experiments revealed that short-term fasting prior to CTX is able to decrease CTX-induced toxicities without affecting the therapeutic effect. The explanatory model of the fasting-dependent protection of healthy cells is that they enter a state characterised by reduced cell division and resistance to multiple stresses during low energy supply. Recent clinical pilot trials showed feasibility and safety of various fasting regiments, and provided first evidence of potential effectiveness.

Objectives:

The aim of our ongoing pilot trial is to investigate whether fasting reduces the incidence of CTX-induced toxicity. Furthermore, the trial examines whether a ketogenic diet as a fasting supportive diet reduces the fasting-related discomfort during the first days and increases the compliance of our fasting regimen.

Methods:

The study has a randomised controlled cross-over design. Gynaecologic cancer patients receiving CTX with a minimum of four cycles at a 3- to 4-week interval are randomised to fast for 96h during half of CTX-cycles and to consume a normocaloric diet during the other CTX-cycles. Fasting is a 4-day modified fasting with a caloric intake of 25% of each patient's daily requirement. In addition, half of the patients should eat a 6-day normocaloric ketogenic diet prior each short-term modified fasting period. The ketogenic diet – a very low carbohydrate and high-fat diet – is known to have a hunger-suppression effect. CTX-induced toxicities, fasting-related discomfort, quality of life, fatigue, laboratory values, and compliance are assessed on each CTX cycle.

Preliminary Results:

To date, recruitment is completed, 121 patients fulfilled the inclusion criteria, and thereof 51patients were randomised to one of four intervention groups. Until the middle of this year 30 patients will complete the study. Of the dropouts, only two patients discontinued the trial due to fasting related discomfort. All patients met feasibility criteria. Results of the analysis are expected until the end of 2018.

Conclusion:

First results of this trial confirm that modified short-term fasting is safe and feasible for gynaecologic cancer patients, however high motivation for fasting is required.