Two more misses

A few weeks ago in the Guardian, I encountered an article with the intriguing title The epic battle with cancer’s Death Star.  I correctly assumed the article would talk about KRAS, the protein that’s mutated in my cancer.  The subtitle suggested that “Forty years after the mutant genes that cause the deadliest cancers were discovered, drugs that target them could be approved”.  I dropped everything and basically ate my phone.

The story is well written, starting with the lucky postdoc who identified RAS as an oncogene, a protein that, when mutated, causes or at least accelerates some serious cancers.  KRAS, a variant, is mutated in 56% of all colorectal cancers.  In forty years of effort, the pharmaceutical industry has failed to develop a single drug that is specific for any of the RAS mutants.  The protein is apparently too smooth, without surface features for small molecules to dock onto.

This picture has now changed slightly.  Research has made progress.  Molecules have been identified that bind to one particular KRAS mutant where the amino acid glycine at position 12 has been replaced by a cysteine.  Amgen and Mirati Therapeutics have promising data from clinical trials.  They plan to apply for approval for their drugs.  Reading this far, my excitement had long cooled.  I have a glycine at position 13 replaced with an aspartate.  The drugs will have no relevance for me.  The situation is as bleak as it was before.

There goes the second option.  The third, which I’ve slowly been getting anxious about, is based on the molecular analysis of the liver biopsy.  The idea is to extract tumor tissue (from my liver) and sequence the DNA for common cancer mutations.  Cancer cells have impaired DNA repair processes and thus accumulate mutations as they proliferate.  Most are detrimental.  Cells with these mutations die off.  Some help the cancer grow faster or fight the immune system or invade other tissues or attract blood vessels.  Cells with these mutations will survive better, and the mutations, already known to medicine as cancer-promoting mutations, can be detected by DNA sequencing.

I had tumor tissue taken from my liver in the middle of February.  Since then, I’ve been waiting for the results.  At first, it took a while.  Then my doctor went on a three-week vacation.  When I saw him a day after his vacation, I understand that he hadn’t had the time to catch up on everything.  But he promised to check up on the results and let me know.

He called me on Friday afternoon.  “There are a few new mutations”, he said, “but nothing that would immediately suggest a therapy.”  He said he would send the results to a colleague of his at the university hospital who is more experienced with this kind of analysis but wasn’t too optimistic.  He also promised to give me the results for some digging.  Maybe there’s a clinical trial somewhere that just happens to recruit patients right now.  It wouldn’t be the first time.

One near miss

It’s an unadjudicated problem among stylists of the English language whether narrowly missing a target should be called a near miss or a near hit.  There are good reasons for either phrase.  Near miss is much more popular, but it could be argued that if the miss was near, the target was hit.  Near does, after all, modify something as coming close to happening.  Merriam Webster has an entire page on this question and the curious history behind near miss.  I’ve experienced three near misses myself recently.

Yesterday I finally called the organizers of the MEFOX study in Ulm.  Don’t worry if that doesn’t ring a bell.  The topic featured early in my blog.  Here’s a quick summary:  There is scientific evidence that the common opioid painkiller methadone might have a role to play in chemotherapy.  Papers describing results in mice and human cells were published years ago but never followed up with safety and efficacy studies.

In 2019, the University of Ulm where the initial research had been conducted obtained funding for a clinical study, specifically targeted towards colon cancer patients on their last legs.  It was supported to start around this time last year.  Patients could enroll only if they had climbed down the ladder of available therapeutic options in its entirety.  I was doing way too good back then to qualify.

Things are different now.  I’m at the bottom rung.  Below me is the abyss of unspeakable blackness.  Meanwhile, the expected starting date of the trial is now in the middle of April of this year.  Yesterday, I called and was happy to hear that (1) they are still recruiting patients and (2) I qualify, at first glance anyway.  I sent them a copy of my case history by email.

The trial would be quite a trial.  Ulm is around three to four hours away, depending on whether you drive or take the train.  Treatment would take one day every two weeks, with CT scans and blood work in between.  Methadone is self-applied, as drops, with a pipette, over a few days.  Naively, I thought I could just travel a day earlier and spend the night in a hotel.  This is impossible in Germany where all hospitality is currently closed.  With case numbers rising sharply, this is not bound to change either.

Then there’s the question of paying for the treatment.  With no big pharma supporting the trial, I’d need my Swiss health insurance to release money for treatment abroad.  They’re already getting nervous when you want to leave the kanton.  Many questions to answer, but I was getting excited.  An option is better than no option.  Now it turns out there’s no option after all.  Today, the leading physician wrote to say that I don’t qualify after all because of my allergy to oxaliplatin, a drug that will be part of the treatment.  Too much risk for them, I guess.  No hit on target for me.

To be continued.

Reality check

Last week wasn’t a good one.  The previous post makes this quite clear.  I worried myself into a hole that threatened to swallow me.  How I was feeling didn’t help but my state of mind was much more fundamental in this.  I don’t think I’m going to die this week or next.  There’s still too much life inside me for that.  On Sunday afternoon I grabbed myself by the collar of the shirt I was wearing and yanked myself from bed.  There’s nothing to be gained from wallowing in self-pity all day.

The jolt of energy kept me going for the rest of the afternoon, through dinner and through the late evening.  I had my afternoon tea, played with the children until temporary exhaustion (mine, not theirs) and, at night, typed up the previous post.  It had been in my head and on paper for days already, just needed copying and shaping up.  Then it got the Friday timestamp because it reflected reality on Friday.  I simply had no energy for it earlier.

Eating continues to be difficult for the most part.  I just don’t manage to put enough inside me.  Sometimes I chew and chew and realize that normally, swallowing is automatic.  For me, it is oftentimes not.  During many meals I must make an effort to swallow, to get this mash down into my digestive system.  Sometimes I wonder what sustains me at all.  Then I look at my arms and legs and am frightened.  They have shriveled to little more than skin and bones.  The 400-calorie drink I consume each night cannot compensate for what I don’t eat.

On Sunday night I took an ibuprofen a couple of hours before going to bed.  I expected my back to hurt and wanted to see if I could avoid or at least mitigate the issue of sweating in bed.  I failed.  I could feel how I was getting hotter as the night progressed.  When I went to bed, everything appeared to have reverted to normal, but at some point I awoke in my usual pool of sweat, pyjamas dripping wet.  Thank goodness for the guest room with its extra bed.

This morning, I went to see my regular doctor for the first time in four weeks.  He had been on vacation.  It’s not that the substitute hadn’t done a good job, but the doctor who’s familiar with your case is a better person to discuss the important questions with.  Here’s what we talked about.

• I had been concerned about the cancer growing despite the current chemotherapy.  My doctor waved a quick CT off.  “We need more time to get a clear picture”, he said.  “Let’s do two or better three months of therapy.”  I liked the optimism in that.
• What about my blood?  My hematocrit value hovers just above 30.  Around 45 is normal.  I had 20 when I was diagnosed with cancer.  Should I be getting iron?  Maybe vitamin B12 again?  “No way”, he said.  “Maybe EPO or a blood transfusion, but it’s not really a big deal”.  What about the rest of it?  My heart races at 100, my lungs work overtime.  “You are more sick than you were half a year ago”, was his sobering reply.
• What about the sweating after taking ibuprofen.  “This can happen”, he said and prescribed me a different painkiller to try.
• Are the results of the mutation analysis ready?  This is the only avenue for unexplored therapies.  He checked his computer.  No, there was no information.  Here I got a bit cross.  It’s been six weeks since the stern radiologist had punctured my skin and retrieved two tissue samples from my lung.  “This is important”, I reminded him.  “It’s the only chance I have left.”  He promised he would have the results by next week.

So it’s really just a question of carrying on, with stubborn insistence in my body and hope in my heart.  There’s nothing else to do.  Pain will come and go, good days will alternate with bad ones, suffering will make way for moments of joy.  It’s all within expectations.  To avoid (or justify) another collapse like last week I asked the doctor explicitly, “Do you think I will die within the next two weeks?”  “I don’t think so,” he said.  It’s an opinion to build on.

No more fun

After a wonderful Tuesday, the week progressed in a terrifying way.  On Wednesday and Thursday, I was out of energy again and confined to the sofa or the bed for long stretches of the day.  I tried to get some work done but my brain wasn’t helping much.  On Wednesday night, I had to give a presentation at a virtual conference organized by a large facility at the East coast of the US.  Luckily it was only ten minutes.  I did all right.  Unfortunately, the conference was so interesting that I stayed up much longer than I had planned listening to the talks.

I’ve spoken before about the feeling of being out of energy.  It seems to me that this time is different.  It’s not just out of energy.  I feel almost lifeless.  I lie in bed wondering how (and for how long) things will continue.  I don’t feel strong pain, but there’s diffuse pain in my lower back that certainly contributes to how poorly I sleep at night.  I’ve tried fighting back with painkillers but paracetamol is no good, and ibuprofen makes me sweat like crazy when I pop the pill in the middle of the night.

I wrote in the previous post that I assumed the sweating had to do with the immune system finally doing its job and getting all pumped after the ovid shot.  This hypothesis fell apart when essentially the same thing happened the next couple of nights.  I pop an ibuprofen.  The pain goes away quickly.  I fall asleep happily, only to awake in a pool of sweat a few hours later.  Flucha found an explanation only about dilated blood vessels and such, but to me it makes little sense that a drug that’s supposed to lower your temperature makes you sweat like a sauna.

Besides the back pain, there’s pain in my abdominal region.  It’s much more disturbing though it’s not very strong and doesn’t bother me much physically.  It’s where the cancer would cause pain if it were growing.  I am currently on chemotherapy, though I’m not taking any pills at the moment.  I’m in the second recovery week of the first Lonsurf cycle.  Has the drug helped at all?  It’s easy to think it hasn’t.  There are scratches on my left side, halfway up my torso.  There are bites on my right side and sharp claws making a mess with my insides in between.  It’s as if there was a rodent living inside me.  In all likelihood, it’s the cancer, and it’s making itself felt.

I don’t know this, of course.  It would take a CT to see what’s really going on.  But when I listen inside me, what I hear doesn’t give me much room for interpretation.  It fills me with negativity.  The current therapy is the last one in the books.  What if it doesn’t work?  What are the steps for me after that?  Do I just wait and watch myself being eaten from the inside?  What happens when the liver fails?

I walked to town today to pick up a prescription.  This little walk, not even four thousand steps, was already too much for me.  The miserable weather didn’t help, but it wasn’t the cause either.  I had experienced something similar when my lung was full of water.  I had to stop and rest at the train station before I could make my way back.  This time is different.  I’m still short of breath and wouldn’t want to climb 200 steps, but stairs were not a particular problem.  Everything was a problem.  I simply didn’t have the power.  I was reaching my limits of performance.  At the pharmacy I was grabbing the counter like an anchor to hold myself upright and give me some energy for the way back.

Life is draining from me.  This spring (or summer, if I make it that far), I won’t be pulling a trailer with two kids along the river in search of a picnic spot or a place to swim.  I won’t even be riding behind Flucha doing the pulling, though the speed would be much more moderate, laughable even for my former self.  I’m not my former self anymore.

My heart rate used to be in the forties when I was in the shape of my life.  My rather sedentary lifestyle in London had taken this up to 60, which is normal.  When I was last in the hospital, for the bacterial infection in my bloodstream, I clocked in at nearly 90, resting in bed.  The other day, I measured more than a 100.  What is my heart racing to achieve?  How can I live like this?

Life is about enjoyment, about having good times, about having fun.  I’ve hardly had a drop of alcohol since before Christmas.  I drink very little coffee.  It’s not that these things make me feel worse.  They just don’t give me any pleasure anymore.  I don’t enjoy the taste anymore.  The moment to take up cigars has definitely passed.  Life is no fun anymore.

Back from the dead

After the covid shot on Friday, I had expected life to continue just so.  Instead, it seemed to end.  I spent Saturday, Sunday and Monday largely incapacitated, entirely out of energy and in increasing discomfort.  I was lying haplessly on the sofa and in bed most of the time.  I thought the end was nigh.

Since I had stitches and occasional other pain from where lung and liver are, I didn’t blame any of what bothered me on the vaccine.  I had read that I should expect a bit of fever, maybe chills, consistent with the immune system working hard to turn a few molecules of RNA into antibodies against the coronavirus spike protein.  There was a bit of that but not much.  With pain coming from lung and liver, my explanation of why I felt so shitty was that the current chemotherapy wasn’t working, and that the cancer was growing out of control.  Not a nice thing to consider.

Last night, I woke up in the middle of the night.  This has become normal recently.  I wake up, turn from one side to the other, and go back to sleep.  Sometimes I get up.  This time, I did.  I had a bit of water and went back to bed, but I couldn’t fall back asleep.  My back hurt in a way that I couldn’t suppress no matter how I positioned myself in bed.  Getting increasingly frustrated with my body, I did something I normally don’t do.  I popped an ibuprofen.

Whether because of the drug or the placebo effect, the pain dissipated quickly.  I found comfort and fell asleep.  It wasn’t the most restful night, though.  From time to time, I half awoke, realizing each time that I was sweating quite a lot, and dozing back off.  In the morning when I got up, I realized that my pyjamas were completely wet, as if I had played indoor football for an hour.  The sheet and the pillowcase were like sponges after a bath.  The most curious thing was I was feeling great.

It was as if I had been reborn, as if the previous three days hadn’t happened.  I was fresh like a daisy, ready for a great day.  The difference to the weekend was mind-blowing.  On Sunday, I refused to paint Easter eggs with the children because I didn’t think I could hold myself upright on a chair long enough.  This morning I could have gone to the forest to collect the twigs from which to hang the eggs.  Maybe it was the vaccination after all that had taken me down.

First shot

Yesterday I got my first covid shot.  It came as a bit of a surprise.  I had registered online three weeks earlier but didn’t expect to be called until April.  Switzerland is a mess with the vaccinations.  Everything happens extremely slowly.  Less than 10 per cent of the population have been vaccinated.  Some in the highest-priority group are still waiting.

I got a text message on Thursday with an appointment on Friday.  I took my doctor’s not confirming my risk-group status and my yellow vaccination passport.  It would make sense, it seemed to me, to enter the vaccination into this little booklet, recognized as it is internationally and underwritten by the World Health Organization.

The Swiss health system has other ideas.  My vaccination passport was ignored.  Instead, I got a simple piece of paper, signed by a person of little leverage, that confirmed that I had been vaccinated.  As proof of its official nature, the piece of paper carried the logo of the Baden hospital where I had received the shot.

How far does the authority of this document reach?  If I tried to travel to Japan or China, would I be welcomed as a healthy and safe visitor, or would I be laughed out of the country without having been allowed to enter it in the first place?  It came to me that it’s ridiculous that the WHO doesn’t issue an app that serves as an official vaccination record.  All the various national discussions about vaccination passports would be moot, and people would have something of wide, maybe global acceptance.  Or maybe Bill Gates should have added little RFID chips to all the vaccination doses.  Then I would just need to touch a sensor at the airport, and all would be good.

So far I don’t feel any side effects from the vaccine.  My harm hurts a bit around the point where the needle went in, but this is minimal.  The cancer has a much graver effect on my well-being.  Even though I’m at the end of the first recovery week, my abdomen hurts from constant pressure, my belly is not too enthusiastic about food, and I am horribly tired most days.  The second cycle of the Lonsurf therapy will start in a week.  When I’m recovering from that, after Easter, I’ll get my second covid shot.

Out of nowhere

It’s Friday already.  The week is almost over.  It was my second week on trifluridine.  What a week it was.  No comparison at all with the week before.  I felt much better throughout.  I didn’t need to puke.  I didn’t spend entire days lying in bed as if I were already half dead.  I got tired by the evenings, but that seems to be the new normal now.

This was all rather lucky because Thursday was a special day.  About a month ago, Flucha floated the idea of getting married.  There was not much of a reason.  We’ve been happily living in sin for many years.  No obvious motive why we would do it now.  Yet I quickly agreed.  I don’t believe in marriage but saw the wisdom of it.  Who knows how things will develop.  Being married makes our family stronger and more secure, and will make everything else simpler and more straightforward.

Getting married in times of corona is a little different.  Currently, Switzerland allows only up to five people to hang out together indoors.  With my mom and the two mandatory witnesses, we had already reached the limit.  My father wanted to come join us despite staying home throughout the pandemic, but we had to refuse.  There was no reason to think bigger.  Instead, we thought small, as small as possible.

The smallest possible wedding entailed a couple, a city official, two witnesses, a short speech, two vows, an exchange of two rings, and a kiss.  It was over within fifteen minutes.  Flucha had put some effort into her outfit and looked truly special, like an extra from a movie depicting the glamorous 1920s.  It was easy to see a bride in her.  I had spent a day rummaging through my clothes to find some without holes or excessive scuff marks.  I think I looked quite presentable as well, though maybe not exactly like a bridegroom.

The happy couple, tightly cropped.

After the non-ceremony, held in a hall that used to be the chapel of a medieval monastery, we had a little reception at home.  Flucha had purchased Luxemburgerli for the occasion, I contributed a Crémant d’Alsace, and mom had decorated everything.  My sister had come up with a big surprise.  She had booked an alphorn player to come down from Lucerne.  He played a few songs beneath our balcony, entertaining the neighbors and surprising passers-by who couldn’t see him.

Now, with a thin gold band around my ring finger, life continues as before.  The disease is making itself known again.  Today, I feel much worse than the days before.  It seems as if the drugs have accumulated through the week.  Maybe subconsciously I pushed myself harder than I should have the first four days.  In any case, today I am deadly exhausted, at one point falling asleep on the sofa while listening to the Toten Hosen.  Tonight I will take the last dose and then enjoy 16 days of recovery.

Short and sweet

The recovery period is over.  It was quite remarkable.  I felt much better on Saturday already.  I had the distinct feeling of getting better as I was lying in bed on Friday night, but that can’t possibly be true.  Sunday was also good.  No pain from my belly.  I ate almost normally though not normal amounts.  I still lacked energy and spent good time on the sofa or in bed, but I got out to go on little walks.  My stomach somehow went back to feeling continuously full, even when I’m hungry, but my body has learned to handle this better than in January.  Conclusion:  The weekend was ok, much better than expected.

Yesterday, I went back on Lonsurf.  The doctor’s words didn’t offer clear guidance.  Did I feel all right, or did I not?  I was somewhere in between.  There was room for improvement, but maybe that’s the new normal.  I decided to continue with the full dosage, as prescribed.  After all, the main point, easily forgotten among all the feel-good blah blah, is beating the cancer.

Today I went up to the hospital to see, wait, no, not my doctor but a substitute.  My doctor is gone for three weeks, vacation.  He seems to take quite a lot of time off.  He was gone around Christmas as well.  But he’s also often in the hospital on weekends and works way past dark.  Good thing that he can compensate the hours that are not in his contract and return fresh, alert and on top of his game.

The substitute doctor did the same things the regular doctor does, but there were some differences.  Sounding out my lungs with her stethoscope, she claimed that they sounded much better than she would have expected from the state of my health as documented on her computer.  She then asked me to breathe in and out deeply.  Today was the first time in months I did this without coughing.  These are the little things that can brighten my day and keep me going.