Earlier this month we announced trial results showing that giving patients with colon cancer (bowel cancer that originates in the colon) a short course of chemotherapy before surgery, could significantly shrink their tumour. This makes the tumour easier and safer to remove, potentially reducing the chances of it coming back.
We caught up with trial leader Professor Dion Morton, a surgeon based at the University of Birmingham, to find out when patients might begin to benefit from this potentially exciting advance.
How has bowel cancer treatment changed over the years? And what challenges still exist?
Happily bowel cancer has transformed from a disease that’s largely incurable and diagnosed at an advanced stage – often as an emergency – to a disease that is largely curable.
There have been some enormous successes in cancer that start in the rectum (rectal cancer), and we’re now starting to see some equivalent advances in colon cancer.
And this has been due to advances in surgery, but also the introduction of new chemotherapy drugs, up to now given after surgery, where we’re trying to reduce the residual ‘micrometastases’.
And what exactly is a micrometastasis?
In practice, there are two reasons why a cancer might not be cured. One is because the main tumour bulk, what we call the primary tumour, is incompletely removed. The other is that the cancer has spread cells around the body. These cells aren’t detectable initially and we refer to those as micrometastases.
So what’s next?
What we’re now trying to do is take that to the next stage, by combining the improvements in surgery with the improvements in delivering chemotherapy, by giving the chemotherapy before the surgery and hopefully making the surgery more successful.
This is done for a number of reasons. Because the chemotherapy has the potential to shrink down the primary tumour, it can make it easier and safer to remove the tumour. Chemotherapy also has the potential to reduce the chances of parts of the tumour being left behind after surgery that might regrow, and helps treat the micrometastases at the earliest possible stage, before surgery.
Why hasn’t this approach been tried before in colon cancer?
That’s a very good question. The main reason is that, historically, the chemotherapy that we’ve used in colon cancer has been less effective. In recent years, the introduction of new chemotherapy drugs has improved response to chemotherapy – from about 1 in every 5 patients to as high as 3 out of 5 patients responding.
The second reason was that if we don’t remove the tumour at an early stage, there’s the potential that it will continue growing until it blocks the bowel, which is a potentially major complication.
And the third concern was that the right patients – the ones who we could be confident would respond to chemotherapy before surgery – couldn’t be accurately identified.
But advances in radiology, chemotherapy and early diagnosis have now addressed all these points, making the delivery of pre-operative chemotherapy possible for the first time.
And so that’s how the FOxTROT trial came about?
Yes, and it’s the first time that a trial of chemotherapy before surgery for colon cancer has been performed as a formal multi-centre trial anywhere in the world.
We’ve already completed and reported on the first 150 patients entered into the trial. And I’m delighted to say that there are now over 400 patients in the FOxTROT trial, which seeks to recruit a total of 1050 patients over the next couple of years.
The report on the first 150 patients has been very encouraging and we’ve shown that there is substantial tumour shrinkage, and a reduction in tumour spread through into the adjacent lymph nodes around the tumour. This makes the chances of curative surgery substantially higher.
Importantly, the trial has also shown that we have selected the right patients for chemotherapy. And crucially we’ve removed their tumour without any additional risk to the patient as a consequence of them having had a portion of their chemotherapy before their operation.
When might we be able to start offering pre-operative chemotherapy more widely?
Really that now depends on the successful and rapid completion of the FOxTROT trial. I think it’s fair to say that the safety data that we’ve been able to provide through the first 150 patients is very reassuring to the clinical community.
But within the next three or four years, we should have the data that will allow us to go forward to providing chemotherapy before surgery more routinely. This, of course depends on whether the full results of the trial prove that this approach really can help.
And finally, what inspired you to pursue a career in cancer research?
I think as a surgeon who’s treated patients with colon cancer over the last twenty years, I’ve seen substantial advances in our ability to cure this cancer. I’ve also seen the arrival of ability to carry out the surgery with less injury to the patient by using approaches such as keyhole surgery (laparoscopy).
And now with FOxTROT we have the potential to improve things further by ultimately reducing the size of the tumour to make the surgery safer and more effective.
So historically, when I started, the cure rates for colon cancer were about 30 per cent, or three in ten. We’re now in a position where more than five in ten patients (50 per cent) with colon cancer are cured, and I’d like to think that over the next five to ten years, that cure rate will rise to over seventy-five per cent.
So I’ll potentially have seen a doubling or even a tripling of the cure rates for this disease over my working life. I think that would be something I’d look back on with great pleasure and to feel that I had contributed to it would be a great privilege. So I think that’s really been my driver all along.
- Interview by Ailsa Stevens, Cancer Research UK press officer, November 2012