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It’s time to write the Lonsurf Diary.

To quickly recap, I was signed up for 3 cycles. Cycle 1 started January 11th 2017; cycle 2 on February 11th, and cycle 3 on March 11th. Each cycle lasts 28 days so the final day would have been around April 8th.

Since my bowel and liver surgery in August 2009, I’ve had three previous experiences of Chemotherapy. First was an adjuvant treatment with intravenous Oxaliplatin and oral Capecitabine lasting from Oct 2009 to Mar 2010. Then, there was FOLFIRI plus Cetuximab (both i/v) from Feb to Jun 2014. A drug trial combo of AZD6738 with Carboplatin (again, both i/v) followed one year later, from Feb to Jun 2015.

Each regimen brought different side effects. With Oxaliplatin, it was neuropathy and neutropaenia (low white blood cells). Cetuximab brought an acne-like rash all over my face and torso. Carboplatin and/or the experimental drug also lowered my white blood cells and platelets.

But none of these were really serious, as measured by my ability to do normal things like working, walking, and eating. No constant nausea. No hair loss. No mouth ulcers. No loss of appetite.

For the 2014 and 2015 sessions it was the same pattern. The first CT scan, done around three months in, would show a positive “progression-free” result. The next scan would show the cancer was progressive again and chemo would stop. Scans done after that have continued to show progression as the tumours get larger.

My most recent scan from early April showed the tumor growth had stabilized. When I initially asked for Lonsurf, I calculated a 2% chance of being a “super-achiever”, and around a 20% chance of getting any sort of positive result. As far as I know, I am one of six patients who have recently received Lonsurf at my hospital. I’m the only one with a progression-free result. That supports the statistic and makes me the “lucky one”.

Unfortunately, it also came with lots of tiredness / fatigue, reduced appetite, and nausea / vomiting. Although I managed to stay the course for each of the three cycles, my white blood count was dropping sharply. I ended up in hospital with (yet another) infection, and stayed there for 4 days at the beginning of April. After massive amounts of i/v antibiotics I felt good again. When they discharged me, I told them I had not felt this normal since around October of last year.

So, what to do next? This is the familiar ground of chemotherapy, in which increased progression-free survival is not such a benefit since it comes with toxic side-effects. I made the decision that I would ask for a break from the drug. To use the title of the David Jones first world war poem, I would become In Parenthesis. There will be another CT scan in late June, with results in early July, and we shall see then.

In the meantime, I’ve resumed my cryotherapy sessions back in Thoracic Park. One thing absent from the CT scan results was any mention of tracheal and bronchial lesions. They have done a great job cutting these out or reducing them. This will continue “for as long as I want them to do it”. I do.

It’s a tricky decision on the Lonsurf. After reading the obituary of Robert M. Pirsig, who died recently, I was reminded what he wrote back in 1974:

“The test of the machine is the satisfaction it gives you. There isn’t any other test. If the machine produces tranquility it’s right. If it disturbs you it’s wrong until either the machine or your mind is changed.” (Zen and the Art of Motorcycle Maintenance)

My body is my machine. It didn’t feel right. I need to take pause.

I guess I saw this one coming – was sent home today without receiving a dose of chemo because my blood platelet count was too low.

Digging out my old posts from December 2009 / January 2010 reminded me they measure platelets as ‘bits’ per cubic millimeter. The normal, healthy person has between 150,000 and 450,000, which is simplified to a platelet count between 150 to 450. They will not administer chemo if it drops below 100. When they tested last Thursday, it was 91. But the hope / expectation was that it would creep upwards between then and today (Monday).

Instead, it dropped to 66. That’s a personal best (PB) for me. Back in the day, the lowest I got to was 78. It would be a very good idea if I did not cut myself shaving at the moment. It might bleed for rather a long time. As I said back then, below 50 and you don’t need a wound. You bleed spontaneously.

The cause of the low platelet count is of course the chemo received, but also (presumably) interaction with the AZD6738. Even though I feel no adverse effects, something is going on in there.

They invited me back on Thursday to take another test. Seemed a bit of a forlorn hope, to get to 100 from 66 in four days. And a journey of 3+ hours there, 3+ hours back. We settled on the idea that I go instead to the local hospital and ask them to do it. *Walks in off street, approaches the reception desk. “Excuse me, would you take some blood from me please?”*

I also found out over the weekend (cheers, Google) that Fragmin can also decrease the platelet count. Apparently, drop below 50 and you have to come off it anyway. That’s the end of me taking that, then. Wish they’d thought that one through earlier and suggested stopping it to me, before I did the search for them.

It does feel so very, very deja vu. I’m stuck in the Evernow. We are on repeat.

Fuck me, but I’m bored of this cancer now.

I’m bored of looking at the charity posters that invite me to join the fight against cancer and the enemy within. Over forty years ago, none less than Richard Nixon  declared the war on cancer. He took a little time off from bombing Vietnam (and cutting medical research budgets, including cancer research) for that one.

Pacifism has always made sense to me. If war is the answer, it must be a stupid question, and all that. Since I became a cancer thingie, my urge not to hurt or kill anything has gone up even more. Atrocities in war zones now depress me more than ever. Those people don’t have to die, yet they are dead.

So why would I want to fight a war against anything, cancer included? It offends me. I’m as offended as someone who goes on Twitter to complain that Facebook is down and YouTube has blocked a video, and that is Mighty Offended Indeed.

Cancer is not within me. Cancer is me. Just as chemo (my friend) is really my destroying angel, killing all that it touches. Cancer is not my enemy. Cancer, who knows where you end and I begin? Cancer might well be quoting Shakespeare at me: “Then hate me when thou wilt; if ever, now“. Do it now. But, I can’t.

I’m willing to take the time to help find out more about drugs that might cure cancer. But I can do it without the war metaphors for cancer. I may have the scars, but I’m not some foot soldier fighting on anyone’s front line, aiming at the unseen enemy.

If, dearest cancer research fundraiser, you make us your soldiers in the war on cancer, then what are we to be called when we fail?

Let me tell you about the “war” that we’ve fought for over 40 years now. The big “battles” we’ve won have come from better screening and prevention, and not from any arms race developing better, more potent drugs.

I’ve spoken before about the essay in “Sightlines” by Kathleen Jamie – the one in which she describes the highly-magnified pathological images from a 10-inch sample of cancerous colon. At that scale, they are like imaginary landscapes. A map of rivers and deltas; inlets and peaks. She also talks about her scar ( a consequence of her breast cancer) and coins a new word “Frissure“. It’s a portmanteau of “frisson” and “fissure”. The fissure (cuts or tears to the skin) part is easy. The frisson (shiver or shudder) part comes from the shock of a scar on naked skin.

And yet, still, there is beauty within. Even as you shudder.

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.