Newer isn’t always better
In advance of International Clinical Trials Day, Emily Hourican reflects on taking part in a cancer drug experiment with an unexpected result
ISUSPECT that culturally many of us are prejudiced against the new, believing the best writing, painting or composing has already taken place. Not so with science, medicine and technology.
There, we are addicted to innovation, convinced that better is always ahead and the best is yet to come.
Probably we are right, but not in every detail. This is something I have had reinforced for me through a clinical trial I took part in back in 2016 when I was being treated for mouth cancer.
I don’t often think back to that time (only when something untoward happens, like an unexplained lump or pain that sends me spiralling back into hysterical ‘what ifs…’). But when I do, I have a series of diaries I wrote for this paper to refer to, should I wish.
Here’s what I wrote about the trial at the time: “I have agreed to take part in a clinical trial, to see if there is a viable, perhaps less toxic, alternative to the current treatment. I will be randomly assigned either
chemotherapy or a different, newer drug. Once assigned, I will know what I’m getting, but the actual choice is up to the universe. And, although both are highly effective in treating the cancer, there are pros and cons to each in terms of side-effects.”
My participation in this trial was brought up at an early meeting with my consultant, before treatment began. The purpose of the trial — called the De-Escalate HPV Study — was explained to me: to establish whether an immunotherapy drug (Cetuximab), had fewer side-effects than the standard treatment of chemotherapy (Cisplatin), delivered alongside 35 doses of radiation. It was conducted by Warwick Clinical Trials Unit, and funded by Cancer Research UK. I would be randomly assigned either Cetuximab or Cisplatin and, once assigned, I would know what I was getting — random, but not blind.
Saying yes to the trial would mean I would help, in a small way, further the cause of medical knowledge and cancer treatment. It also meant there would be another level of care afforded to me as I went through treatment, another team of people to monitor and look out for me.
Before saying yes, I talked to heaps of medical people — any consultant or doctor I could get my hands on. The responses were very similar. Everyone I spoke to said they would favour chemotherapy over the newer drug, because of the established body of evidence behind it. But they all also said if a clinical trial was offered, they would take it.
I did take it. I liked the idea of ‘paying it forward’ in terms of some of the misery I was going through. I was persuaded by the idea of even more care. And, by the time I came to be assigned, I was positively hoping to get Cetuximab.
I hated the idea of chemotherapy, with its sledgehammer approach and known toxicity. I didn’t want to lose my hair and this wouldn’t happen with the Cetuximab — although, I was warned, I was likely to get severe skin reactions, including acne and mouth ulcers. Basically I wanted the newer drug because I believed it would be the better drug.
And I got it. I had six doses of Cetuximab, given intravenously over six weeks alongside the radiation. They were right about the skin reaction — within three days of the first dose my face had erupted into a thousand painful spots.
This was ‘good’ I was told — it showed I was responding to the drug. I continued to respond — by the end of treatment, I had third degree burns to my neck and a mouth full of ulcers. But that was OK. It was in the name of science.
Fast-forward three years to now, and the results of the trial have just been sent to me.
Turns out that newer isn’t always better. The results are clear as a bell: Cisplatin is “significantly better” than Cetuximab, both in the two-year overall survival rate (97.5pc for Cisplatin, 89.4pc for Cetuximab), and the two-year recurrence rate (6pc for Cisplatin, 16.1pc for Cetuximab.
In addition, there is no significant difference between the two in terms of severe toxicity.
That, I have to say, was a bit of a facer. Honestly, despite the legal warnings around the trial (something along the lines of those ‘value of shares may fall as well as rise…’ that you get with financial products), it never actually occurred to me that what I was taking might not be at least as good as the traditional alternative.
Hopefully these findings don’t, really affect me any more, because I am past the two-year window in which recurrence may happen.
I am, or should be, home free. But I am very glad I didn’t find this out earlier. Because it would have scared the living daylights out of me.
The conclusion among medical professionals is that this trial has been a success, because it provides “definitive information about the comparative effectiveness of treatment choices” (this is a quote from the president of the National Association of Laryngectomee Clubs).
“It is only through research like this that effective treatments can be honed.” (That’s from the communications officer of Heads2gether, the UK national head and neck cancer support group.)
A friend, who also happens to be an eminent medical man, said: “This is the very reason we do these trials. The fact that the result was unexpected suggests that the trial was well-conducted.”
Or, as Eibhlin Mulroe, chief executive of Cancer Trials Ireland, put it: “Every cancer trial is important. Every trial adds to the overall knowledge base. Each piece of new knowledge or confirmation of existing knowledge is like finding another piece in the puzzle and takes us closer to finding better ways to prevent, treat and cure cancer.”
And I get all of that — indeed, I am pleased to have been a small part of research that clearly will benefit patients who are unlucky enough to get the cancer I had.
But, if I am honest, all of that is within the context of the fact that I am not — thank God — one of the unfortunate 16.1pc who had a recurrence of their tumour. Or indeed the 10.6pc who did not survive to the two-year mark. I am simply not that good a person.
I’m glad I took part in the De-Escalate Trial, because the outcome has been positive for me, and because I fully understand that, without trials like these, there is no reliable way to test important new possibilities. But it’s also a timely reminder innovation doesn’t always mean progress.
‘It never occurred to me what I was taking might not be at least as good as the traditional alternative’