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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.

Chemo drugs such as carboplatin work in cycles. That’s true for the side effects too such as low blood counts. The “nadir” is the lowest point of the cycle and it usually occurs 21 days after infusion. The only slightly better news is that recovery starts after 28 days.

On my Nadir Day I could certainly agree. Voice gone down to a croak, weary as fuck, and kidneys so knackered it made me look up the word “nephrotoxicity” in the dictionary. And Carboplatin is there, implicated as a cause of all of them.

But at least it was the nadir of cycle 4 and it’s the last one. Things can only get better, right?

Then came the phone call with the results of the last CT scan. The scan showed an increase in the upper right node from 23mm to 28mm. Not huge, but significant and evidence treatment did work briefly but has now stopped working. The doctor said that because my voice had not recovered he would refer me to an Ear, Nose & Throat specialist. They would study with camera etc. He told me they also found that my kidney / bladder connection is distended (explains a lot) and he will refer me to a Nephrologist for that.

I would not even bother mentioning the blood platelets were it not for the fact they’d recorded a staggeringly low count of 36.

We spoke about the voice and whether it was a tumour pressing. He told me they cannot see from scan if that’s the case but one of the nodes shares space in the mediastinum with nerves for vocal chord so they cannot rule it out.

Today I saw the ENT doctor. After a quick Laryngoscopy (the one where they look at your vocal cords using a thin, flexible tube down the nose), they were able to tell me my left vocal cord is paralysed. Something is probably pressing on a nearby nerve, causing it to seize up. Well, it just gets better and better.

There is some hope. Apparently they can “plump” or “bulk” up the paralysed vocal cord with body fat, collagen or another filler substance. This makes it bigger so the other vocal cord can touch it and trigger that wonder product of vibration that we call speech. I’m going to volunteer that they sacrifice my fat arse for the plumpest left vocal cord, ever.

But first I have to wait for the consultant to call me, maybe.

This is not a happy place. The trial drug only seemed to produce low platelets. We get reminded again that any chemo may work once briefly but cancer quickly adapts to overcome it. And now there is a new threat – living without the quality of speaking.

The doctor talked about future trials but I said “it depends on trial”.  To be more honest than I was with him, it feels like I am done there and my new battle is to get my voice back.

In the 1930s the novel written in Irish typically told the story of the noble Islandman. He stood resolute against the battering Atlantic storm, with a stout and honourable heart that dearly loved his God and his neighbours. Adversity was but a passing challenge to be scooped up in the fishing nets of his wisdom. Morality was simple. Books written “for children or nuns” indeed.

The genre was fair game for Flann O’Brien / Myles na gCopaleen in 1941 in “An Béal Bocht” (“The Poor Mouth”) which satirised the whole Gaeltacht existence thing. The non-hero is Bónapart Ó Cúnasa, and he is a pretty miserable, self-pitying individual, living in constant calamity. Misadventure falls on his misfortune. There is but a fine line between him and the family pig. He’s so feckless they had a “feck” mountain left over and they’ve had to recycle them into Irish comedy up to the present time, just to use them up. If it wasn’t for the mad schemes of his old man, the Old-Grey-Fellow, the family would be on hard times altogether. For feck sake (that’s another one).

Although published in 1941, The Poor Mouth didn’t appear in English until 1973. Just in time for the New Ireland. They’d sentenced me to twelve years of compulsory Irish language learning, so inevitably I became monoglot in English.

Another novel , “Cré na Cille” by Máirtín Ó Cadhain, appeared around the same time (in 1949) but has only just been translated by Alan Titley as “The Dirty Dust”. I urge you to read it. I’ll come back to the translation of the title another time, but a stab at pronouncing his name would be something like “Maur-cheen Oh Kyne”.

I never stood a chance with it being in the Irish, and myself the monoglot. But I was not going to pass on the translation of any book that was initially rejected because it was too “Joycean”.

You see, the whole thing takes place underground, in the dirty clay of a cemetery, and the novel is a dialogue between the dead. But maybe “dialogue” is too grand a word. It’s more of an ongoing shouting match as each dead voice struggles to be heard. And what do the dead talk about? Mostly about the petty squabbles they had going on up above. The dead can talk, and they never let up for a second. A few of them went to their death expecting a quiet time of it after, and they are especially aggrieved at the outcome.

It’s not an easy book to read. If it was the text of a play, you’d have Mercutio: or whatever next to the lines to help you follow. This is just a stream of unattributed babble where you have to pick out the speaker from the text. You either learn the characters or you may as well give up. But this has the effect of speeding up the flow, so it really is like listening to a room full of Irish people talking. We have to use phrases like “Listen to me now” or “Come here to me now” just to get a bit of attention for the next utterance, half-blind to the irony that these filler words add yet more noise and even less signal.

Each character in Cré na Cille has a distinctive voice. Catch-phrases, if you like. It makes me smile to remember my own family and the phrases they made their own. It would be like you’re in a pub in Galway and you’d run into the aunt and the uncle out for the night:

Is that yerself that’s in it? Nice mouth on ya for a pint of Guinness. Were you up the country saving the hay? Ach, no better man! Who’s yer man abroad there? Nice mouth on him for a Mercedes and the trousers hanging off him. Far from class he was reared. Sure, fuck the begrudgers. A decent skin, all the same. No better man! Are ya coddin’ me? Wasn’t it him that was after telling me his self? Some cute hoor right enough. No better man, me arse! Fair fucks to him though all the same. No better man! You’re grand. Will ya take another one? Good on ya, sure you might as well. No better man!

The great thing about all of this and the encounter in general is that you would not have to utter a single word. It would all just stream around you whether you wanted it to or not. Good times.

The bitter irony of the ability of the dead to speak is that I myself can barely talk. I’m as hoarse as a crow that’s been eating sawdust in a desert. I’m the raven in Macbeth that can’t even portend the death of Duncan. That’s how hoarse I am. It started just after the chemo in cycle 3 and it has lasted for weeks now. The doctor said it was either an infection (unlikely, no temperature, etc.) or it was a tumour pressing on a nerve. Not so good, that second option. Think on the irony if these tumours are being kept stable in size, but one of them still finds a way to wreak havoc. The doctor gave me an apologetic smile and a prescription for some antibiotics. The drugs did not work.

On the strength of a useful suggestion I started to think of a third reason for the hoarseness. Maybe it’s the chemo? Could Carboplatin cause hoarseness or changing voice? That’s a search phrase right there if ever there was one. There are several mentions of the possibility in the results, but if you go by the numbers then the occurrence rate is something like 0.002%. Not the most heartening of statistics.

I went back on May 14 for what was called a “discontinuation” meeting. It just means it is coming to the time they will stop me on the study drug trial, but it does sound like a Joy Division song – when the procession moves on and the shouting is over. Here are the young men, indeed, with a weight on their shoulders.

It was a bit of a farce. Yet another doctor I’ve never spoken to before, glancing at my notes like a cheat sheet as we spoke. After he got it wrong on the number of cycles and the name of  the drug trial I’m on, I gave up inside. It can all be a little tiresome some times, when you think that I’m meant to be their guinea pig on the important research that will Cure Cancer. At least I had a CT scan the same day, which justifies the journey, and he made the useful suggestion that they should scan a little more intently around the throat region. So it came to pass, and I should know the results next week.

Anyway, I’m finally in Cycle 4 (the last cycle) of my drug trial treatment. Days I feel the “chemo-wipe” wash over me – waves of fatigue your worst feelings of tiredness, listlessness, and weariness ever, all coming together at once. Make my bed I’ve a pain in me head and I want to lie down. But there’s an Irish proverb:

An rud nach leigheasann im nó uisce beatha, níl leigheas air.
(If butter or whiskey won’t cure you, there’s no cure for it)

So, bring on the butter and the whiskey, and hope in the cure for the croak. I’m not quite ready for that old sweet ground, where so many weary souls take their rest.

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.