Metronomic chemotherapy actually doesn’t have a really straight, good definition. It’s defined as giving lower doses of chemotherapy with a frequent schedule and without extended breaks. So it’s basically opposed as the way we used to give, or we still give, chemotherapy which is the biggest dose than we can but spaced out. By changing the schedule and the dose you get different effects. So, instead of directly killing the cancer cells because the drugs are cytotoxic, you target the microenvironment of the tumour so you inhibit angiogenesis, you restore the efficacy of the immune system. And there are some emerging data that shows that you may also target the so-called cancer stem cells. On the other hand, you also decrease the side effects so basically you don’t have neutropenia, you almost don’t have nausea, vomiting, patients don’t lose their hair so it’s also very patient friendly. We tried generic treatments that are oral so they don’t have to come to the hospital for the IV injection of chemotherapy. Also, one thing that is important is that instead of aiming at having responses, so tumour shrinkage, sometimes we think that just being able to maintain a stable disease but for a longer period of time is another option, another interesting outcome.
You’re making the disease chronic?
Sometimes we manage to do so, yes, but I guess we’d rather aim at controlling for a long period of time than having a response but for a shorter period of time.
In what stages of cancer is it used?
We can’t say it’s really like the mainstay right now. It’s still somehow niche so the most frequent uses are for frail patients, in palliative care because it’s a good balance between potential efficacy and side effects, and as a maintenance.
But it’s used in a metastatic setting?
It can also be used in a metastatic setting, yes.
But not in early cancer?
Can you tell us a little more about the Metronomic Global Health Initiative?
We actually launched the Metronomic Global Health Initiative with Eddy Pasquier and Marc Le Menestrel to try to promote the use of metronomic chemotherapy and drug repositioning for children with cancer living in poor countries, what we call now low and middle income countries. The fact is that in high income countries we diagnose only 20% of the children with cancer but we have good results. We reach almost 80% of cure. While in low income countries where 80% of the children with cancer are, the outcome is not as good because we have basically a 25% chance of survival. There are some specific constraints or limitations like they cannot afford expensive treatment, they don’t have sophisticated infrastructures where they can use central lines and inject the chemotherapy. Sometimes these patients are under-nourished so they cannot tolerate the toxicity of this treatment. So initially we thought that maybe that oral, inexpensive with low toxicity treatment could be an opportunity to generate and propose treatment for these patients.
Do you have some ongoing examples?
Yes, there are some experiences that have been published in Mali, a lot of work has been done by Professor Banavali in India, and we’re trying to help starting new studies to try to see which regimens could have some activity on new patients that have too advanced disease to tolerate standard chemotherapy or who relapse. So we’re helping to open these studies in Morocco, Brazil and India.
Because these are the countries, the developing countries, where cancer is forecast to increase dramatically?
Exactly. Actually the birth of global oncology, as we call it now, is when our authorities realised that the number of patients with cancer would increase dramatically in low income countries and we had to do something about it.
Where does your funding come from?
At this very moment we manage to get funding from grants, national grants. There are also some philanthropy affiliations that will actually give us some money to help us. But at the moment we were more focussed on building the network, raising awareness more than raising money. So I guess we’ve started stage 2 where we’ll just go and try to get more money to be more effective in helping people setting new projects.
What about drug repositioning in this context?
Drug repositioning consists in using drugs that are not known for being anti-cancer agents but, through research, realised that they have anti-cancer properties so they can be used as anti-cancer agents. The advantage of these drugs is usually they are used for chronic disease so they can be taken orally for a long period of time, they’re not too toxic. Some of them are generic so they’re cheap and some of them also have a very specific mechanism of action like targeted therapies actually. So by combining drug repositioning to metronomic chemotherapy we can generate what we call a metronomics protocol that actually allows us to introduce target therapy or therapy with a smart mechanism of action to poor people.