Two years maybe, probably not five“, is the sort of prediction you might get from a frank-speaking Oncologist, if you pressed them hard enough (as in, very hard indeed) to give you a prognosis for your life expectancy with cancer.

It’s funny/peculiar how different blocks of time appear to us. Two years is very short. Five, not much better. If you were told “five years, probably not seven” you’d probably take a completely different approach. You’d get on with something else and come back to really worrying about it when it was further along. Probably when there was two years left.

When approved treatment options are exhausted, it becomes a gamble. An experimental drug on an early phase trial could change the prognosis, maybe extend the two years to four. That sounds so very attractive, and makes it much closer to my second example prognosis.

But, it isn’t that simple. Those two years are not equal in their quality. It’s not a cliff-edge at the end of two or three years, then total sickness leading to death. It’s a downward linear progression. The first six months of the two years is better quality time, in terms of health, than the next six months, and so on.

If I assume that January 2015 was month 1 of my two years, then I had a decision to make. I’m being offered a Phase 1 trial that will combine a new drug with an older (chemo-)therapy, to see if the combination is more effective than either alone. The chemo is a platinum-based one, and they believe that my ‘best period’ was that time between February 2010 and September 2011 when I had completed a series of platinum-based chemo cycles. That was nearly two years extension, and if this new drug could achieve the same result…

On the other hand, 2015 is probably going to be my “quality time” in terms of symptom severity. A round of four chemo cycles and a new drug with unknown side effects could change that dramatically for the worse. Allow six months to fully recover from it all, and whoosh! there goes 2015…

“More detail. more detail”, you cry. “How can we evaluate without more detail?” Fair point, well made. Let’s see if we provide some.

The drug is called is AZD6738 and it is to be administered orally in combination with a cytotoxic chemotherapy regimen using Carboplatin.

A tiny bit of science first. Between 50 and 70 billion cells die each day in the average human adult. The process is called apoptosis, or programmed cell death, and many pathways and signals in the cell are involved with it. Cancer genes stimulate cell proliferation, and cancer cells do not naturally undergo apoptosis. The reason why they can’t be programmed to die is because various proteins involved in the signalling pathways stop cells from being able to kill themselves.

Cancer treatment by chemotherapy and radiotherapy kill target cells primarily by inducing apoptosis. But the efficacy of these treatments, as I’ve said before, diminishes over time and use. Some protein or other seems to get in the way, and is adapting to the ‘new threat’ of apoptosis.

ATR and AKT are examples of protein kinases that promote cell survival through various pathways. These proteins in cancer cells tells them to carry on growing even when they have been damaged by treatment (such as chemo or radiotherapy).  ATR senses DNA damage and activates a damage checkpoint, which arrests the cell cycle destruction process. If you could suppress this, the survival mechanism is suppressed and the cell dies as intended. In effect, you are inhibiting the inhibitor. A sort of double negative that results in a positive.

The drug in question, AZD6738, is an ATR inhibitor. It was discovered in 2013.

So, you kick off a blast of apoptosis with a chemo such as Carboplatin, and you stop the ATR getting in the way of destruction by using AZD6738. You start with a week-long cycle of AZD6738 by itself, so any bad side effects are isolated and can be attributed to that drug alone. They then envisage four cycles of chemo should be enough, and on a 21 day cycle that is four months of therapy, give or take a little.

There is a lot of monitoring required. Partly because the procedure is untried, and partly because it is a trial and requires data gathering. It is roughly two days per week, every week, for the next eighteen or so weeks.

Of course, there are side effects. Chemotherapy causes apoptosis, but too much of that causes white blood cell generation to be suppressed in the bone marrow. Too little is like inducing HIV/AIDS, and leaves you prone to infection by degrading your immune system. This particular chemo is often most associated with neutropenia (decrease in white blood cells).

Then there are the likely side effects of AZD6738, which appear to be: increase in heart rate and contractions, damage to gut lining, change in immune system, increase in liver proteins (a sign of damage), and swelling  of the duct in the testes or ovaries.

My experience is there is always a “headliner” when it comes to side effects. In my first chemo, for example, it was that nerve reaction called neuropathy. For this one, I’m envisaging a battle to keep my immune system from falling below an acceptable level. If I fail, there will be many low-grade but debilitating chest infections, and the like. It’s practically a certainty that at least one chemo cycle will have to be delayed until white blood cell count is restored. It could be a rough few months.

What would be “success” in all of this? If my body was a failing Company, then you’d measure it by a turnaround in fortunes and a return to profitability. By that standard, it would be prudent to say that the chance of success in this trial is around 10-15%. But, medicine doesn’t count it like that. If nothing happens and my condition stays exactly the same, then success is also declared because the progression of the disease has been arrested. Given that “stays the same” has a probability of maybe 75%, then success is Practically Guaranteed. I’m being a little cynical here. If I do nothing, the probability that it will stay the same is also high.

So, it comes down to whether I volunteer for the trial and run the risk of making myself very sick, thus ruining maybe a quarter of my precious two years; or whether I focus on staying positive and as healthy as I can, so that I get the most from those six months.

I had to decide, so in the end I signed the consent papers a week or so back and now I’m on the trial. The first cycle begins on Monday.

This week I had a CT scan as part of the trial preparation. My last one was in September 2014. I had to make my decision not knowing the results. The scan showed there was worsening of the situation. The tumours have enlarged slightly and one lobe in the left lung has collapsed under pressure. There was nothing new. I would not describe this as “staying the same”, so I feel a tiny bit more sure in my decision to participate now.

Différance is a French term coined by Jacques Derrida. It’s described as a mixture of delay and deferral. In my case, the delay is the awareness that it is now too late to do anything about my cancer. The deferral is the awareness that it is too early to do anything about the end-state that the cancer will bring me to. Yup, some might say I got Différance.

It’s why I keep quoting T.S. Eliot, e.g.:

Go, go, go, said the bird: human kind
Cannot bear very much reality.
Time past and time future
What might have been and what has been
Point to one end, which is always present.

It’s the present all right, and this bloody Différance means I have to do something.