Role of metronomics in cancer clinical trials and practice in developing countries

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Published: 19 Jul 2013
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Prof Shripad Banavali - Tata Memorial Centre, Mumbai, India

Prof Shripad Banavail talks to ecancer at the 2013 WIN Symposium about treating cancer patients in India, where most people do not have health insurance and have to pay for drugs out of their own pocket.

This means most can not afford treatment which is the standard of care in wealthier countries.

Metronomic therapy (repetitive low doses) can help with this situation; moving away from newer drugs towards 'drug repositioning'; using older cheaper targeted drugs alongside chemotherapy - often 3 in combination that target:

1) the tumour itself

2) the tumour microenvironment including angiogenic effect

3) the body's own immunity

Filmed in Partnership with the WIN Consortium

WIN Symposium 2013

Role of metronomics in cancer clinical trials and practice in developing countries

Prof Shripad Banavali - Tata Memorial Centre, Mumbai, India

We’re here at WIN and you’ve given a very nice presentation on treating cancer in developing countries where there’s a cost problem.

Yes. The average cost of any new targeted therapies now is in the range of $5-10,000 a month and if you see the average income of an Indian patient will be less than $1 a day. So in that respect, actually, we have to consider how we can treat this patient and there’s no insurance in India unlike in Europe and in the United States where cancer care is taken care of mostly by the insurance and third party payers. In India 90% of the time the patients have to pay from their pocket so whenever we think of treatments then we may develop a very effective treatment but if it’s not actually affordable patients won’t take it. Like I’ve shown in my talk, the simple example of using Herceptin or trastuzumab, which is used for HER2 new positive breast cancer patients, when we analysed the data in our hospital out of the 411 eligible patients only 8% will be treated with the drug, half of them because they were on trials. So actually only 4% of our HER2 new positive patients could afford to take a drug which is a standard of care in most of the Western countries. So that is why we want to say that if we develop any treatment for these low and middle income countries it has to be affordable to be effective.

So what type of treatment do you think could be affordable?

You know, there’s a lot of biology, a lot of science, available there in the literature, in the clinics so we have to be. What we have done is used all the science and how we could use it for our patients. What we are propagating at present is the use of metronomic therapies along with the standard therapies; I’m not telling you to go away with the standard therapies. The standard therapies which are called the maximum tolerated dose therapies because they are given every three or four weekly, they have their importance, you have to use them effectively but along with that what we propagate is the use of these low dose metronomic therapies, especially in two settings in the curative form. One is in the perioperative setting, that is after the surgery is done in solid tumours, we introduce them at that stage, and very, very importantly as part of maintenance therapies.

What we are doing at the Tata Memorial Hospital is we are going away from the drug discovery mode. In the West, actually, they can afford these newer drugs so they are going after drug discovery which is very important to have newer drugs for treatment. However, what we are doing in the Tata Hospital is we are going after what we call drug repositioning. That means there are many drugs which we are already using, for example we are using a number as an anti-angiogenic drug or metformin as an anti-mTOR inhibitor. Then we have HDAC inhibitor, so there are many drugs which are already there in the market which we’ve used over the years, they’re very low cost, we already know the side effect profile. So we’re using these drugs effectively along with our chemotherapeutic drugs in the metronomic setting in the sense we say that we do not have to target the tumour alone. Like in targeted therapies, most of the time it targets only the tumour cell but what we see in metronomic is along with the tumour you have to target the tumour’s microenvironment and also the body’s immunity.

So the metronomic therapies that we propose is a combination of three, at least two or three, drugs wherein one drug targets the tumour, another one modifies the microenvironment including the anti-angiogenic effect and the third drug usually modulates the body’s immunity because that also plays a very, very important role if you want to improve the long-term outcome of a patient. This combined, when we are done, that we assumed some excellent results and most of the therapies that we have developed are by using the drugs which are already on what we call the WHO essential drug list. Why is this important? Because, one thing, they are cheap and the second thing, once they are on the essential drug list they will be available in every country. So using it that way we have developed really some low-cost protocols which usually cost not a dollar but even less than a dollar a day and have made much improvement. However, what we need now in the future is basically we have all this retrospective data, now we are planning to do really level one science, generate level one scientific evidence, in the form of doing randomised trials using the pilot data and adding along with that what we call the biomarker studies and other biological studies and show that this is not only possible but basically they have scientific evidence also. So that’s what we have to generate now to get accepted by the oncologic community.

In the Tata you’ve set up the Metronomic Consortium.

Yes, after the initial data that we presented initially there was a lot of scepticism whether it works but now with the data that is getting generated over the years that we have been working with this a lot of interest has been developed in the field of metronomic therapies in the hospital. We have founded a consortium wherein we have clinicians taking care of various types of patients – lung cancer, head and neck cancer, ovarian cancer. Most of the cancers we have developed management groups in the hospital so we have come together as clinicians and along with that we have what we call the Advanced Centre for Cancer Research and Treatment which is a research wing where we have multiple principal investigators working in different fields. So what we have done is we have combined together the clinicians and the researchers, including the pathologists, the radiologists, the nuclear medicine people. So together we have formed a consortium wherein we’ll be doing various clinical studies and along with that we’ll be answering the biological questions along with that. We even have help from the Global Metronomic Health Initiative which is an organisation formed by Dr Nicolas André from France and he is also helping us out with designing various studies. So it’s a consortium not only of various clinicians from the hospital and from the country but also we’re getting some international support.

Are you in any way involved with WIN?

WIN, basically the Tata Memorial Hospital, being one of the bigger tertiary cancer centres, is already part of the WIN consortium and when we actually discussed about the metronomic data in the forum, actually it was when we sent our data, preliminary data, to the scientific community they found it important enough to be presented as an oral presentation here and that’s how I got involved. This year that Tata Memorial Hospital has been one of the initial members of this WIN and has been consistently represented in the WIN consortium over the last five years.