Optimum duration of adjuvant treatment of stage III colorectal cancer: 3 versus 6 months

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Published: 9 May 2019
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Prof John Marshall - Georgetown University Hospital, Washington D.C., USA

Prof John Marshall speaks to ecancer at the 2019 International Gastrointestinal, Liver and Uro-Oncology Conference (IGILUC) in Cairo about the treatment of stage III colon cancer after surgery.

He describes the adjuvant use of fluorouracil and oxaliplatin in patients with colorectal cancer.

Prof Marshall also discusses the evidence that support the use of these drugs for 3 months of therapy versus 6 months.

In terms of impact, he believes this data gives oncologists a new standard to use to optimise and personalise treatment.

 

Stage III colon cancer has been with us since I’ve been an oncologist and that’s a long time. The general standard has been after surgery to give somewhere between six, maybe even twelve, months of chemotherapy. If the surgeon pulls the weed we treat the yard with medicines to prevent any new weeds from growing and that’s called, of course, adjuvant therapy. When it was just 5FU that was easy because 5FU is an easy drug, you can give it for a long period of time without much in the way of cumulative side effects. We figured out that six months was probably about the right amount of time where you got the most benefit from that.

Then came along this other drug called oxaliplatin and oxaliplatin has cumulative side effects – the more doses we give the more nerve toxicity you get. We were giving twelve doses of the stuff and, in fact, almost everybody with twelve doses got bad nerve toxicity. So we needed to figure out could we give less. A huge study, global effort, 12,000 patients, half of whom got three months of chemotherapy the other half got six months and the basic punchline was that three months looked about as good as six for almost all patients. Even in the very high risk stage III colon cancer patients, they were pretty close with just a little bit of difference for the additional three months.

Now, the debate that Dr Axel Grothey and I had, we were assigned sides, was is three as good as six? Really, yes, it is. I lost the debate in some ways but I also tried to win it by cheating because even with our current standards many people are dying of their cancer. So with the drugs we’ve got now, or the approach we have now, three months is as good as we’re doing. But we are far from done because many people with stage III colon cancer are dying of their disease despite these drugs. So I made the argument based on a new paper that looked at even longer treatment, so not six months but twelve months of treatment, in fact, did better than six months of treatment. So maybe we should think a little bit like they do over in breast cancer land where they give hormone therapy for ten years after a breast cancer diagnosis and begin trying to fix those other people that we have yet to cure with stage III disease.

What do you think will be the impact of this study?

The IDEA study showing that three months was pretty much as good as six months gives us a new standard. If nothing else it gives us big data to be able to show an individual patient how much do you get out of three months, how much more would you get out of another three months of therapy. It gives us permission to back off from our treatment.

For oncologists one of the very difficult things for us to do is not give enough treatment because we worry that if their cancer does come back was that our fault for not having them given enough treatment versus it was going to happen anyway. So, most importantly, this study allows us to back off on our treatment, optimise, individualise, don’t cause neuropathy in your patients with stage III disease.

What it doesn’t tell us for sure is whether or not this is translatable to stage II disease, to rectal cancer, to when we remove a metastasis from surgery, is three months good enough for those situations too? We’ll never do those studies; in my mind I think they do translate to those settings but we will have a debate about that.