Concluding the debate around dexrazoxane

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Published: 15 Nov 2017
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Dr Etienne Brain - Institut Curie, Paris, France

Dr Etienne Brain talks to ecancer at SIOG 2017 in Warsaw.

He discusses dexrazoxane and it's use to counteract the effects of anthrocyclines, and the difficulties in detecting the cardiovascular toxicity they cause.

The debate is whether dexrazoxane affect the efficacy of the chemotherapy.

He also discusses the age range it could be used for. 

This service has been kindly supported by an unrestricted grant from Janssen Oncology.

The use of dexrazoxane was a bit conflictual for some years because of some restrictions in terms of labelling raised by the EMA and FDA. Actually this is one of the different options we have in hand to counteract the side effects on the heart of anthracyclines which are really strongly potentially toxic but also at the same time strongly active in many diseases, solid tumours as well as haematological malignancies. What is difficult with anthracyclines is that from the beginning, from the first milligram that you use in a patient, you hit myocytes and you create kinds of damages which are irreversible and which start very early. It’s a bit like frailty in the older patients, it takes time to unveil really what happens. So that means that because you do not assess any practical consequences on the left ventricular ejection franction that you do not have any damage. So any attempt to prevent or to limit these kinds of side effects is important.

Dexrazoxane is one of such possibilities, we have other ones like long infusions, like cardioprotectors as well, controlling high blood pressure is also a very big point. But what is true is that some of these preventive measures are easier to handle than others and dexrazoxane is really something which is easy, it’s indexed according to the dose of anthracyclines that you use, and it’s very active, it’s very productive in terms of protection.

The concern which has been long in the mind of oncologists was does it affect the efficacy of the chemotherapy. But, there again, the last update in terms of data provided to EMA, submitted to EMA, shows that these kinds of concerns do not exist anymore. So it was a big relief in terms of use. I don’t expect that it’s going to change immediately the way that we use it because it takes time, we’ve got habits, maybe it’s a wrong attitude because they are still very important drugs, these anthracyclines. But I would say that it will take a bit of time. For the elderly population it’s clearly something which is important because of the higher sensitivity of the heart and cardiac function to this kind of damage.

Who should dexrazoxane be used for?

When you consider that almost 30-40% of patients older than 65 have high blood pressure and that it’s the first risk factor for cardiac failure, it is really a wide volume of patients who are potential candidates for such preventive measures. What is really intriguing is that we have some meta-analyses which have investigated the role for such preventive measures in terms of cardiac issues and they’ve shown that it works quite well.

Why do we not use it more often? That’s a question in the way we analyse the literature, especially for the elderly. I would say that certainly because of that older than 65-70 women or men requiring the use of doxorubicin for lymphomas, breast cancer or other disease, really are very good candidates to avoid the development of such failure which when it happens is really one which has a worst prognosis in terms of  issue. You do not cure, you do not catch-up this kind of situation when it happens. The global outcome is one year of survival behind with this kind of cardiac failure induced by anthracyclines.

Any advice for clinicians about dexrazoxane?

I would say that we do not have a very good signal or sentinel diagnostic tool to identify the damage that we create up front with the use of anthracyclines. That’s what makes the slippery into cardiac failure so touchy and difficult, tricky to screen for. So any use of anthracyclines should really put clearly in mind, we should hold that in mind, the balance between benefit and risk that we take. I would say given the high predisposition of older patients, older people, to cardiac failure it should be considered much more often than what we do. Dexrazoxane really doesn’t have any safety issues or activity issue on the anti-tumour efficacy of the treatment. So I don’t see any reason why it shouldn’t be considered more often.