Phase 1 trial is they don’t know what the results are going to be. They don’t know what side effects you’re going to have. They don’t know how well it’s going to work, whether it’s going to work. It’s got to be started somewhere, and [sighs] if, if the phase 1 trial does work on some, they might be able to adjust it to do a different, using the same drugs used in a different way. I actually found out this morning that the dacarbazine could actually be given in tablet form as well, which I didn’t know. But it’s very, very expensive in tablet form, so obviously money does, money obviously comes into it, so that’s why it’s done as a intravenous one. But [sighs] you know, we’ve got to start somewhere and you can only do so much on animals. You don’t ever know what’s, what the human body’s going to do. You know, I look back, when I knew it was a phase 1, and thought of the four chaps that almost died, which was a phase 1 trial*, and thought, No, you know, it’s closely monitored, very closely. Because the first two treatments they were taking blood tests every fifteen minutes. It was lots of blood tests so that’s why you were in all day, but very, very closely monitored. And you know, I have been closely monitored. Each time I come there’s ECGs, blood pressure, temperature, urine samples, blood tests.

*FOOTNOTE’ Anthea is referring to a Phase 1 trial at a commercial research unit based at Northwick Park Hospital in 2006 when several healthy volunteers became extremely ill. Early phase studies are carried out precisely because we need to find out about possible risks and side effects before giving the treatment more widely.

I think it was the idea that I should go for the treatment that was most likely to benefit me, and so the – there was also an element of sort of scientific curiosity. I was quite keen to take part in an experiment, an interesting experiment, and of course pleased if there was benefit to other people. And as time goes by and as I am stable on this drug I’m more and more thinking about that aspect of benefit to other people, in terms of finding out what the long term consequences are of the drug. So if the consultant put it to me that maybe I’d be on the drug so long that all the cancer cells were eliminated and I need no longer continue with the drug, I’d be inclined to say, Well, I think I should continue, because then we’ll find out when the drug is safe in the long term.

Do you know how long they’re, I mean are they just going to give it to you indefinitely at the moment. Is that the plan?

That’s the plan at the moment, yeah.

Okay, yep.

Yeah.

And I think you said the trial is now finished in the sense that they’ve recruited everyone.

The phase 1 trial is complete and so they’re not recruiting for the phase one trial any more.

But there are phase 2 trials going ahead, that is trials which – so phase – I should explain it – a phase 1 trial aims really just to check toxicity of the drug. How big a dose can you tolerate and are there terrible side effects which would discourage you from using the drug? And then a secondary goal of a phase 1 trial is to begin to see whether the drug is effective. But the primary goal is a more basic thing, just toxicity and dosage adjustment.

So that phase 2 trials that are going on now are aimed more at finding out how effective it is in selected smallish groups of patients, and there are several of those trials going on, some in England, some in other countries. More than one drug company is involved, so there are alternative drugs that target this same enzyme. And some of them are restricted to patients with breast cancer, for example, others to patients with ovarian cancer. I am a rarity as a prostate cancer patient with an identified BRCA mutation, and I think at least one of the trials leaves open the possibility of recruiting people like me with BRCA2-dependant prostate cancer.

So this young lady asked me if I would like to take part in a clinical drug trial, and she explained the situation. She says, It might not help you. There’s no guarantee She says, It might help other people further down the line And again she said, You’re a perfect patient for a drug trial, for a clinical trial She says, You’re young, you’re fit and you’re health [laughs]. You know, even I had to laugh – I was young, fit and healthy, the only problem I’ve got is I’m dying from lung cancer, you know.

So anyway, that was okay, so she says, Right, I’ll phone the trials unit and see what I can do So she phoned up, got an appointment there for the following week. Went along and, you know, a medical, a check-up to see that I was okay to take part in a trial, so I was accepted into the trial, which I believe was a phase 2 trial. It wasn’t randomised and as I said, I think I just quite followed, not quite followed the mice, but their tails were just disappearing round the corner.

It was six months of chemo. I was quite fortunate I wasn’t too bad with the side effects. It ended up there was a kind of group of us of four or five. There was about eight people I think getting the drug, but there was about four or five of us always seemed to be at the same point where we were, of getting the course of the drug but we’re at different stages of actual lung cancer. So during the course of that, you know, one was dying, a couple of weeks later another one would die, so it was a case of thinking, Well, you know, whos next? When’s it going to be your turn so to speak.

We were all getting the drug, and there were, the explanations from what I can recall were very good. It was explained again about I can withdraw at any time, if they find I’m having bad effects with the drugs that they’re giving me or, then they would pull me out, because I think obviously they were looking at the quality of life, as well as trying to find out if this drug was effective, you know. I have no complaints about that side of it at all and the nurse, the research nurses who were involved also were very good at explaining, and they would take their time, either if myself, or Helen, or any of the other patients who were there had questions. Some patients didn’t have questions. As usual some people want to know everything and some people don’t want to know anything, some people want to know a wee bit, you know. But because my, I felt whatever was going to happen to me, whatever decisions I was going to take it was going to affect my whole family, so I wanted to know everything, which perhaps maybe made it a bit easier for the medical staff because they knew, Well, Tom wants to know, so we can talk to him, we can tell hi, you know. But I have no – on recollection the medical staff at that time were very good with their explanations.

They were very specific saying that, It is a trial. it’s early days. We haven’t got any result, that a lot of the tests that went along through the process of the trial had been changed, and, and a lot of the blood tests were made more regularly, because it had been trialled in the States and they’d had one person die on the trial through kidney failure because they hadn’t been monitored, they hadn’t monitored the effect as much. So I knew that, and they had, they had made more blood tests available so so they could, they did monitor you very, very carefully, and have been, in all the trials, I’ve been monitored very, very carefully.

And that I think that they have been very, very honest. The doctors have been very honest. You know, that This, this is a trial. We haven’t got any definite results. It has worked on some people but we’ve, we haven’t got a percentage of who it works on [sighs]. And I was told that the chances of the Taxol one working that it was a fourteen per cent chance that that would work. And my attitude was, Well, somebody’s got to be in that fourteen per cent I wasn’t in that fourteen per cent. That one didn’t work. But I wasn’t given any percentages on this one, because it is a phase one trial and I was only number twenty-six. So I knew that it was a very, very sort of new trial, and I was prepared to take that risk.

If there was any chance of stopping the disease, or halting it for any length of time, I would give, I would want to give myself that chance. If I said, No, I don’t want to. I don’t want to do this, I think I could have had regrets, saying, Well, if I’d have done that, perhaps I would have still been here. You know, once you start getting ill, Well, if I’d have done that, perhaps I’d have stood a better chance. Perhaps it would have slowed down the disease. And there would have been lots of ‘what ifs. I’m not into ‘what ifs. I want to be positive, and I think anybody that knows me will say that I am a very positive person. I’ve had lots of knocks. I’ve had lots of things that I could have said, Well, why me? But you pick yourself up, and you’ve got to look to the future. You, you can’t, you can’t look and think, Well, why did that happen? These things, things happen in life. Why me? I’ve done that. Why me? But when I’m feeling, if I’m feeling down then yes I do, do think, Why? You know, Why is it me? What have I done wrong to deserve this when there’s so much going on in this world that it could be somebody else? But [sighs] when I think logically and positively, then I think, Well, yes, it’s got to happen to somebody. It’s happened to me. I’ve got to get on with it. I want to do lots more things in this life and if I’m to do those then I’ve got to take the chance of these trials.

So your main reason for taking part is about taking every chance for your own–

Yes.

–benefit.

Plus the fact it might help – if it doesn’t help me, it might be something that will help somebody else, and if it helps somebody else to save them going through the trauma that I’ve been through, then I’m, I’m happy to do it. If it, if it helps anybody, you know – it might be it might be a friend, it might be a relation, it might be somebody I don’t, don’t ever have contact with or know, or know that it’s helped them – but if I’ve done this and it does help somebody, then all well and good. There’s a purpose to it.

But, as I say, I think I’ve just been extremely lucky. And I should also say I’ve been treated extremely well by the hospital that I went to. So when you start the phase one trial you have to go into hospital for a week while they check on how the drug is behaving in your body. And I’ve always found the nurses and all the staff are extremely friendly and remarkably cheerful. That was the impressive thing about this specialist cancer hospital, what a cheerful atmosphere it had, in spite of the fact that people were often very ill there.

So I don’t know if I should say a bit more about the details–

Yeah, and what it was like.

–of the trial and what it was like.

Yes.

So once the decision was made, then there was an adjustment to be made to my previous hormone targeted drugs, so I stopped one of those. I had to wait a few weeks for that to clear out of the system and then went into the hospital for a week, or maybe it was less than a week, anyway, for a few days, in which time lots of blood samples were taken. I was given the drug. The rate of clearance of the drug from my body was monitored. The response of my cells to the drug was also checked with a clever method that involved plucking hair from your eyebrows and then doing some microscopic staining on it to see what how the cells were behaving and seeing if they were responding to the drug in the way that was anticipated.

And so the first day or two blood samples were taken at frequent intervals, every few hours, so you’d get woken in the night for blood samples to be taken. And then, again I forget all the ins and outs, but roughly speaking after that was over samples were taken at rarer intervals. Then there’s a period of a few months when I had to go once a week to be checked, and after that I dropped back to once a month. So every month I go. I have some blood samples taken. I have my heart function checked because I have some heart difficulties, unrelated to the trial I should say. And I talk to a doctor, not usually the consultant, but usually one of his registrars or assistants. I guess I’m an easy case, because I don’t really have any great problems. And the next day I get the results of my PSA measurements, and they’re quite good about telling me what the results of the tests have been each time.

I should say a bit about side effects. So that’s a big issue if you’re in a phase one trial, especially. So the experience, if you – I’ve seen the summaries, descriptions of how the trial has been going so far. There have been some public talks about it by the people running the trial. And the position is that, very roughly speaking, of the people who you would expect to benefit, that is the people who have mutations in either of these two relevant genes, about half show a good response. Most of the people in the trial have had advanced cancer, so they’ve been recruited to a phase1 trial because other treatments have failed. And that usually means they’ve had quite severe other treatments and quite advanced disease.

So I was peculiar, because my disease had never been very advanced but the two standard treatments had failed in a technical sense, but I hadn’t had anything very severe. I’d just had these hormone suppression therapies.

Anyway, so it’s understandable that not everybody benefits, even if you might hope that they would, because they’d been very ill in various ways, and also some of the drug treatments that they’ve previously had are ones which, as we now know, are liable to lead to resistance to treatment with this particular drug.<

It’s hypothetical and it’s probably difficult to, to answer, but if you were further down the line–

Uh-huh.

–and this was a phase three trial–

Uh-huh

How would you have felt about randomisation and the possibility of being allocated to a group that might not be getting this particular drug?

Well, knowing what I know now [laughs], I would be very uneasy about being randomised to the placebo treatment, because I think there’s strong evidence the drug brings a benefit which you couldn’t achieve any other way.

But, so if I were to be in a my sister always made the point that for most trials the ideal thing was to be in the placebo branch of a randomised trial, because then you got very close monitoring from good medical staff and you were likely to do well because of that. And most drugs, trial drugs, didn’t do you all that much good and might hurt you, so [laughs]. However, in this case it’s not like that, I think.

*FOOTNOTE’ This raises difficult questions about the level of evidence needed before a drug can be said to work. Julian’s personal experience had convinced him the drug was effective in his case. However, although his clinical team felt the drug was promising they also felt there was not yet enough evidence, so they needed to test the drug further in a Phase 2 trial. Sometimes, even when Phase 1 and 2 trials suggest a new drug is promising, when it is compared in Phase 3 trials with the standard treatment in a much wider group of people the results do not show it makes a significant difference. (See ‘Non-randomised trial designs and other research’ and ‘What are clinical trials and why do we need them?’).

If – this was an experimental treatment and you could only get it if you took part in the trial. If this had been set up as a randomised trial where you might get it or you might not, how would you have felt about taking part in that?

Oh, I would have gone for it definitely. Oh yes. If there was some treatment available which would be helpful, then I would definitely take it.

And how would you have felt if you’d been randomised to the group that didn’t get it?

Would I have known that is was the group that didn’t get it?

You might or you might not – depends whether the trial is blinded or not.

Mmmm, [sigh] well, I suppose it’s a bit like entering a competition and not winning. I’d have felt, Well, that’s just the way the cookie crumbles. It would have been helpful if I’d had the trial. If I couldn’t have the trial, then hopefully there’s a different treatment that could deal with me. But with this particular trial it’s been going on for a long time, and it’s very well established, and it will eventually, hopefully sooner rather than later, for the benefit of other people in my position, be approved by NICE [National Institute for Health and Clinical Excellence]. And hopefully it will be available in hospitals, so people don’t have to go through that terrible, terrible stress of deciding to pay for a treatment and then being landed with the whole of the costs of the NHS, which is diabolically unfair. Because when you have cancer it’s very stressful, you don’t need the added stress of the financial worry. That is really a life sentence. I feel that if the people who are in charge, all the bureaucrats, if they were in our position they wouldn’t behave like that. And I really feel that so strongly. And if there was something, you know, one could do about it, like petition or something – I know there are doctors who are very involved and being very cross about it as well, and doing something about it.

I suppose that what they would argue is that they don’t yet know whether it’s safe and whether it works, and that that’s what this trial is trying to find out before they make it available to everyone.

Yes, I’m sure that’s right. But it is, it is available. It’s available in America, and the Americans, of course, have a very good track record of cancer treatment, better than here, as I understand it.

Mmm, so there is some evidence actually over there?

Yes absolutely, absolutely. And also I think with this particular hospital I’m at and with the consultants I’m under, they wouldn’t recommend anything that wasn’t appropriate. Because there’s another thing – people can take the same drug but the side effects can be different, because everybody is different. People can react differently. The way the drug reacts on your cancer can be different, one person to another, so that’s another thing. It’s all very complicated.

Footnote’ Licensing for use in the UK was approved in July 2008 shortly after Pam’s interview.

Well, that was on the morning of my operation. I went in the night before. It was a little bit more vague, because it was just, the ward was hotter than Hades, it was just so hot. And I hadn’t slept well and the bed was uncomfortable. And they’d said, You mustn’t have anything to eat or drink after midnight And then in the morning it turned out I was third on the list, so they said it would be about half one by the time I had the operation [laughs]. Then the breakfast trolley came round and I thought, Oh God

And I had a headache. And then she, the, I think she was a registrar anaesthetist suddenly appeared and said that they were doing a clinical trial on a new device to, it was a camera to put down your throat to see whether, the improvement in sore throats afterwards. And also it gave them a better view of the larynx. And so I quickly read through it and said, Oh yes, that’s fine Because I thought, Well, if I’m under an anaesthetic anyway, frankly I don’t really mind And if it’s something that gives them a better view of everything, then if there was any problems anywhere they would, they would be able to pick it up. So again it wasn’t a huge decision to make. But she did go through it all and there’d already been a study in Pakistan and Gloucester [laughs], which seemed odd, but yes, and she said that it, she’d, so far it seemed that things were improving. But it just seemed such a minor thing that frankly I didn’t mind at all.

What about the timing of that? Because that sounds like you were feeling quite vulnerable already at that point. Was it a good time to raise that or should it have been discussed at a different point?

I think, I think that was fine for what it was. If it had been something, you know, more, that I felt would have had more of an impact than that. But like I say, if you’re under anaesthetic anyway it can’t be that different to what they’re already doing. They’ve already done it on eight hundred people so, yes, it was fine. And then she came after the operation when I was just coming round and said, Hows your throat? Is it sore And it wasn’t sore, so that was it.

So that’s partly what they were looking for?

Yes.

What else were they looking for?

Because they said it gives them an improved view of the larynx and the throat and that type of thing.

And are there any other safety concerns that they’re testing while they’re doing this?

I don’t think so, no. I think it is just a new piece of equipment that they’re trying out.