My study is focused on advanced ovarian cancer patients. We know that the majority of ovarian cancer patients arrive at advanced stages and in many cases they are not suitable for primary cytoreductive surgery but they need neoadjuvant chemotherapy followed by interval debulking surgery. This results in some cases 50% of the population, so it’s very important and the real challenge is to increase the rate of response to neoadjuvant chemotherapy.
Could you outline the methodology?
Our study was a phase II randomised study, a pilot study focusing on advanced ovarian cancer patients unsuitable for primary cytoreductive surgery, so requiring neoadjuvant chemotherapy with carboplatin and paclitaxel, followed by interval debulking surgery. In the study we randomised patients to receive either short-term fasting or free diet. Short-term fasting has been proven to enhance chemotherapy resistance in preclinical models and in our case it was fasting starting 36 hours before until 24 hours after the end of each chemotherapy cycle. We had as primary endpoints metabolic endpoints, so the evaluation of insulin level between the short-term fasting arm and the free diet arm. Then we had other endpoints such as toxicity during chemo and surgical outcomes, survival outcomes. Also we planned some translational analyses. The preliminary data are about immune analysis. There were required that 17 patients per arm to have the right number of patients for these endpoints.
What did you find?
We found that the primary endpoint was met because insulin variation is an important factor. Particularly, we found an increase of the insulin levels in the free diet arm while we found a slight decrease in the insulin levels in the short-term fasting arm. This is important because insulin is correlated with metabolism of tumour growth and also chemoresistance. So this primary endpoint is in favour of believing that there is a positive metabolic profile induced by fasting.
The secondary endpoints were also important because toxicity wasn’t different between the two groups in terms of both haematological and non-haematological toxicities. Currently we are also analysing the quality of life data, the questionnaire that we gave the patients. But for now we can say that this is tolerated and manageable.
We also found an increase of the pathological complete response expressed with something called chemotherapy response score, which is typical of ovarian cancer – 60% in the short-term fasting arm compared with 70.6% in the free diet arm. So there was also a good response which is one of the challenges I mentioned before in the neoadjuvant context. Also there was a prolongation in the median progression free survival, significant.
Of course these were secondary endpoints, this study is not powered, but the meaning overall is that if drugs are crucial for treating our patients it’s also true that probably other factors need to be considered and nutrition could be one of these factors. Our data suggests at this point from the metabolic point of view that there is a correlation between what we eat and effect on metabolism and this effect may have some consequences on cancer growth because we also found some important results in terms of response and pathological response.
So what we have to suggest to our patients tomorrow after this data is difficult to say because these are preliminary data but we have no reason anymore to believe that nutrition has no correlation with tumour evolution. Instead, we have reason to believe that other research should be done in this context. Of course in the context of ovarian cancer but probably also for other cancers. There are some other data, especially in breast cancer but probably we should find the right type of fasting and also the right population. And probably this may be a non-pharmacological approach that may help in improving the cure rate of our patients.
