European Multidisciplinary Cancer Congress (EMCC) 2011, 23-27 September, Stockholm
Synchronous chemoradiation significantly reduces the risk of the breast cancer recurrence
Dr Indrajit Fernando- Queen Elizabeth Hospital, Birmingham, UK
Welcome, Dr Fernando.
You’re about to give a very important Presidential session address on radiation therapy in breast cancer; a big trial and a really, really interesting result. Tell us all about it.
This is a trial that has looked at the sequencing of adjuvant chemotherapy and radiotherapy, something that despite the fact that we’ve been using chemotherapy and radiotherapy for over thirty years, we haven’t as yet had a large trial to look and see whether we can, by essentially using sequencing, to affect the local recurrence of our early stage breast cancer.
So what was the trial design?
The trial design was to compare the standard way of giving chemotherapy and radiotherapy, which was chemotherapy first followed by radiation, to giving it synchronously. By that what I mean is the chemotherapy and radiotherapy is given together, either in a sandwich form so that if you were using, say, a shorter, three week course of radiotherapy the radiotherapy was squeezed in between the gaps between the chemotherapy courses; if you are using a longer radiation fractionation such as a four or five week course of radiotherapy, which is commonly practised in Europe and the United States, then the two treatments were given concomitantly, so essentially the radiotherapy carried on right through one of the chemotherapy courses. What we looked to see is giving it in this manner, did we improve local recurrence and also, most importantly, did we in any way worsen the side effects, toxicity and quality of life for our patients.
Now all these women had had breast conservation therapy to the breast?
No, about half the patients had had breast conservation, the other half had mastectomy but there had to be a clear indication for both adjuvant chemotherapy and adjuvant radiotherapy.
OK. Premenopausal or perimenopausal or postmenopausal?
All age groups were covered.
All covered, OK, and what happened?
The results of the trial showed that if you gave your chemotherapy and radiotherapy synchronously, you produced a 35% reduction in your risk of local recurrence. That is a magnitude of benefit that we have seen when using chemoradiation in numerous other sites, for example cervical cancer, head and neck, lung cancer, a very, very similar effect. And what was also very interesting was that when we looked at long term late side effects there was very little difference.
And you were clearly very glad about this, this hypothesis coming right, but also a little surprised.
I was surprised because if you’d asked me to predict what would happen, I thought we might see a lower rate of local recurrence but we just didn’t know, because the trial had not been done, whether the long term side effects would be worse. Of course we had two French trials using a slightly different chemotherapy regime to the one we used, using a mitoxantrone chemotherapy regime, both of which had shown significantly worse side effects of treatment. So we just did not know, until we got the results from our trial, whether toxicity was worse.
Your chemotherapy was mostly CMF, is that right?
Half the patients, approximately, had CMF, the other half had an anthracycline followed by CMF regimen. At the time the trial was running we were also running another CR UK trial called NEAT trial, which was actually comparing those two regimes, and the two trials actually sandwiched together and you could randomise your patients into both studies. But approximately half the patients had CMF, approximately half the patients had anthracycline followed by CMF.
And the anthracycline group didn’t suffer more toxicity?
Which you might think from the mitoxantrone comparison.
They didn’t because effectively the radiotherapy was not given during the anthracycline part of the treatment. The radiotherapy was given during the CMF part of the treatment and there was no difference in toxicity and also the effect of the treatment was also in both groups. So whether you had CMF or anthracycline followed by CMF, which would be much more the standard treatment nowadays, the benefit of treatment was seen in both groups.
And it’s a powerful study, it’s over 2,000 patients randomised.
Yes, it is indeed.
This is not the sort of sexy trial that gets pharma company support and, in fact, it’s something which I hear frequently from the radiation therapists, that it is very difficult to get practice changed by doing practical studies which impact on patients’ quality of life. Now you’ve done that, who funded it?
This was funded by Cancer Research UK and they funded the entire study including trial co-ordinators, statistical support. We had a small grant from Pharmacia of about £1,000 but essentially we had no drug company support for this, this was all essentially Cancer Research UK.
Well, well done Cancer Research UK, a conflict of interests as the next Chief Executive. Thank you very much indeed, Dr Fernando, that’s a really, really lovely study.
Thank you very much.