DIRECT-2 studies the hypothesis that a fasting-mimicking diet enhances the efficacy of neoadjuvant chemotherapy in patients with hormone receptor positive and HER2 negative breast cancer. – Dr Judith Kroep
DIRECT-2: a phase 3 trial on fasting mimicking diet to improve neoadjuvant chemotherapy in HR+, HER2- breast cancer
Breast cancer is the most common cancer in women worldwide, with over 2 million new cases diagnosed per year. Like most other cancers, breast cancer depends on nutrients and growth factors to continue to grow and to resist and escape current standards of care.
In mice, a fasting-mimicking diet has been shown to protect mice with tumours against the toxic effects of chemotherapy, while enhancing the effect of therapies and boosts chemotherapy-induced effective immune cells.
A large previous study (DIRECT1) demonstrated that breast cancer tumours were more likely to shrink in patients who were short-term fasting using an fasting-mimicking diet. Additional research is needed to show the impact of such diets on cancer treatment outcomes in a larger trial and to discover how the diet works on the tumour biologically.
Aims and objectives
The intervention will aim to shrink the tumour by 90–100% in patients at surgery by using fasting-mimicking diets alongside chemotherapy compared with regular diet.
This study will also aim to understand the impact of a fasting-mimicking diet on the immune cells of the tumour. It will evaluate the impact of the diet on the response rate, on 3- and 5-year event-free survival, and on quality of life and cognition.
How it will be done
Patients with HR+/HER2- breast cancer that needs initial chemotherapy will be randomised to receive their regular diet or a low-calorie and low-protein diet 2 days prior to and on the day of chemotherapy and throughout their treatment period.
Biopsies from the participants will be analysed to understand the mechanism and impact of the diet. MRI scans will be used to look at the effect of the fasting diet on the tumour; ie whether it has shrunk more. Quality of life including cognition will be measured using questionnaires.
If successful, this project will show fasting-mimicking diets to be a novel, safe and effective means to improve the antitumor effect of chemotherapy.
It will also examine the mechanism of action of the diet in the tumour (immune)-cells.
This project will lead to a better understanding and a clear step towards implementation of short-term fasting during chemotherapy for patients with breast cancer as a safe and effective alternative to current diets. It may therefore have far-reaching consequences for cancer treatment in general.