Friday, May 29, 2020

Pain threshold

After watching the first two episodes of Last Dance, the hagiographic documentary on Michael Jordan, I’m pumped enough to masquerade as the Michelin Man.  MJ always goes for the win, doesn’t see losing as an option, doesn’t give up, and sees obstacles as parts of a training course that helps him get even better.

I’ve encountered my share of obstacles over the last eight months.  Most I’ve ignored away.  Some came flying in my face and left me dumbfounded for a while.  They’re still as big as they were when they first hit me.  None of my problems has got any smaller.  But I’m here to fight to make them go away, and I’ll smash them to pieces if they refuse.

In 1998 when the Bulls were gearing up for their sixth championship, I was getting ready to start graduate school five thousand miles away from where I grew up.  My destination was Salt Lake City, home of the Jazz, the team that faced the Bulls in that year’s NBA finals.  The games were shown on a big screen in a club in the city where I went to college.  Thanks to the time difference, tip-off was at 1 or 3 in the morning.  I went to watch a few, the only Utah boy in a crowd of Chicago fans, and clearly remember one game with Michael Jordan sick with a flu, ashen-faced, near collapse during every time out, and putting ball after ball in the basket in the most impossible ways.

I might not have much of a drive to win but, like Michael, I am ready to endure pain when I need to.  That’s probably the only thing I share with him.  If there’s a good reason for it, I’m ready to suck it up and suffer.  This got me through my PhD, and it will now get me through the cancer.

Earlier today I got a call from my oncologist with the schedule for the first couple of chemo sessions.  We’re starting in two weeks, just as I had requested.  The doctor had also discussed the question of which antibody to use.  The conclusion was that the anti-VEGF antibody is fine for now.  We might try the anti-EGFR one next time.

On the question of fasting, there was development I hadn’t expected.  The local enthusiast is all for it.  No surprise here.  But he encourages me to start two days before the chemo and then continue until 24 hours after the part of the chemo that’s done in the hospital has finished.  In effect, he’s asking me to fast half a day longer than I’ve tried so far.  Hard to believe, but this guy is even crazier than me.  This makes me feel taken care of in exactly the way I need.

Fasting for 90 hours a time won’t be easy.  It might be total agony.  But it might also help.  I can’t wait to start the second program.  I might collapse on the fourth day.  But that’s by my own choosing.  It’s not going to be the bloody cancer that will bring me to my knees.

Wednesday, May 27, 2020

Breaking the fast

Fasting is hard, though it gets easier with time.  The third day was once again easier than the second.  I felt no pain or hunger, and managed to focus on work.  I thought of food a lot but mostly in a hypothetical way.  It didn’t distract me too much.  This started to change in the afternoon.  The last couple of hours, when the nuts in my backpack were beckoning, stretched uncomfortably long.

Breaking the fast is also hard.  Muslims celebrate this every night during Ramadan with feasts of dates, tajines and lots of merriment, but they fast during daylight hours only and hardly have the time to get hungry.  If the fast is long, breaking it means getting metabolic pathways back into gear that have entered a state of profound inactivity.

A long fast empties the stomach and the intestines.  The body adapts to a complete deprivation of energy.  All non-essential activities are at a standstill.  Cells stop making things, lying statically in their tissues as if dead.  Protein and DNA synthesis are shut down, as are any catabolic pathways.  It’s like hibernation.

Breaking the fast requires getting everything back into gear, and this takes time.  I stuffed my belly with nuts, a hamburger, an apple, bread, cheese and chocolate.  I easily consumed 2000 kcal during dinnertime.  The nuts alone added up to 900.  My belly was not amused.  The food didn’t sit easily and wasn’t digested smoothly.  It took a while until my stomach had cranked up its activity level to deal with this unexpected bounty.  Until this happened, I felt as if someone had piled rocks into my stomach.  I wonder if there's a better way of easing into this.  It might not matter.  Now, four hours later, I sit on the sofa content and as if reborn.  Life is good again - and maybe there’s a little less of the cancer in me than before.

Whether this is a reasonable hypothesis was one of the questions I had for my oncologist today.  To my delight, I found an unexpected ally.  The doctor didn’t dismiss the potential benefits of fasting.  She said she would not recommend it to patients because the jury is still out on whether it helps with therapy, and there are certain risks that should not be underestimated, but she’s happy to encourage it in patients that raise the topic themselves, as long as they are strong and outwardly healthy.

Best of all, she told me of a colleague who is convinced of the rewards of periodic fasting.  This doctor is known to have said that he’d fast himself if he got cancer.  He’s an oncologist and a bit of a nutrition buff.  My doctor will discuss my case with him and come up with a strategy of how to combine fasting with chemotherapy.  My approach would be to fast for two days and start chemo on the third, but I’m happy to be told otherwise.

In keeping with my current cycle, the first session of the second chemo program will probably start in two weeks.  Twelve sessions will continue through the middle of November.  If nothing unexpected happens, Christmas in Argentina is realistic, from my side anyway.  If Argentina continues on its current trajectory, it might take some time until it’s wise to visit, but six months is a long time.  It will take me a dozen more fasting sessions to get there.

Tuesday, May 26, 2020

Hunger returns

Do they say that the second day is the worst?  They should.  The second day of fasting is substantially harder than the first.  The temptations of food lurk everywhere, especially if you go grocery shopping, which I did to have something to do over lunch.  I was very close to breaking the fast on many occasions.  The nuts I bought are for tomorrow, but I almost ripped the pack open today.  If I can trust the experience of the first fasting session, tomorrow will be easier.

The question of why I am doing this came to my mind many times today.  Life is short (shorter for some than for others, but you never know).  We should enjoy it as much as we can.  Why didn’t I buy an ice cream?  Why didn’t I have steak tonight?  Why didn’t I nibble constantly during the day, keeping my belly happy and my brain flush with energy?  It would have been so easy.

In the newspaper today there was an article about spontaneous recovery from cancer.  Two people were profiled who were in desperate situations many years ago and inexplicably survived.  They’re cancer just disappeared.  This sounds a bit like the beginning of a snake oil sales event, but there’s science behind it.  Or rather, science wants to get behind it.  Oncologists in Zurich have created a database where they collect such rare cases to understand them better and, the best outcome of all, find aspects, treatments or behaviors that many cases share, and that might improve everyone’s chances.

Some of the behavioral factors correlated with positive outcomes are exercise, healthy nutrition, active involvement in one’s treatment, a positive outlook, and the will to live.  This didn’t surprise me.  These would be good habits, even if they didn’t help.  I think I live all of them (though I could eat more fruits).  And it’s the will to live and the active involvement in my treatment that keeps me away from temptation for three days.

At the end of the second day of fasting, I’m a bit more convinced of its usefulness.  The review that got me started on this topic states that “the vast majority of tumours proliferate optimally in the presence of excess glucose”, which I take as meaning they won’t proliferate well when starved.  This is something to build upon.  Some cancers depend on fat as their energy source.  The paper that introduced this concept also starts out by saying that “most cancer cells are programmed to increase glucose uptake”.  Energy requirements are just a minor aspect of this upregulation.  “Glucose in cancer cells tends to be used for ribose production, protein glycosylation and serine synthesis.”  For cancers addicted to sugar, fasting must have a therapeutic effect.

The review makes the very sensible suggestion “to study the metabolic preferences of each type of tumour and to complete preclinical evaluation of the outcome of changes in the dietary energy source before adopting any recommendations for patients.”  I haven’t been given any dietary recommendations specific to the chemotherapy.  I was told to eat as much as possible and as richly as possible after the hemicolectomy but this advice was never updated.  Definitely something to talk about tomorrow.

Sunday, May 24, 2020

Fasting and sugar

It’s been eight days since my last post.  Nothing of note has happened in the intervening days.  My health is stable; I’m feeling good.  Eating normally over the previous ten days has restored my weight.  Everything is set up perfectly to bolster my delusion that everything is all right.

Everything is not all right, which is why I’m starting my second episode of finite fasting tonight.  After a dinner of asparagus and mint risotto with beer (because someone forgot to bring white wine up from the basement and put it in the fridge), I’m now off to another 72 hours without food.  The specialist in Zurich didn’t think much of this approach but didn’t express any serious concerns that I hadn’t been aware of either.  He pointed out the danger of losing weight during therapy.  “Weakening yourself only helps the cancer”, he said.

Helping the cancer is the last thing I want to do.  Fasting appears to stand a good chance of achieving the opposite under two conditions.  First, I have to do it within the limits set by my body (see the specialist’s concerns).  This one is easy.  I have to keep an eye on the bathroom scale and be aware of how I feel.  The second one is trickier and I don’t know yet if it’s met.

The anti-oncogenic effect of fasting depends on cancer cells’ urgent requirement of glucose for their growth.  Glucose is of course a source of energy, but it’s also required for the synthesis of biomolecules that sustain the high proliferation rate of cancer cells. Without sufficient glucose, DNA cannot be synthesized at the levels required by cancer cells.

This is not all.  Consumption of glucose leads to the secretion of insulin, a hormone with oncogenic properties.  There is agreement that glucose contributes to cancer progression and resistance to therapy.  Had I read about this earlier, I would have long cut sugar from my diet.  But does this even help?  The body is a complex system, and individual adjustments are unlikely to yield single obvious effects.  Glucose is the most abundant carbohydrate in human blood, and there’s very little one can do about it.

The benefits for cancer patients of living on low sugar are far from clear.  Fasting isn’t much better.  It has been shown to work in mouse models of certain cancers only.  Is the metabolism of my KRASG13D adenocarcinoma similar?  I don’t know.  I’ve tried to find publications but haven’t been very successful.  (This one is on my list.)  Maybe it’s described in books that I have no access to.  This is important information.

On Monday, I got a call from the hospital to schedule the next consultation for next Wednesday.  On Friday, my oncologist called to find out whether I’d be up to starting the second chemotherapy program right after that consultation.  I equivocated because I would really like to have some answers on fasting, but this is too important a topic to be discussed on the phone.  The doctor didn’t insist.  She correctly took my hesitation as a sign of a need for a little more time.  I hope we’ll have a good discussion on Wednesday.  Even if she doesn’t have the answers, she’ll be better placed to get them than me.

Saturday, May 16, 2020

Lights on

After a barrage of posts earlier this week, when I was getting into the various options of continuing the battle against the cancer, it’s been oddly quiet for the last few days.  After the cliffhanger of the imminent visit to the specialist in Zurich, some might be wondering about updates.  Did the specialist have anything creative to share?  Does he expect a breakthrough?  The cliffhanger continues.

On Friday morning, I picked up a new projector to replace the one that stopped working six weeks ago.  The old one suffered from a broken powerboard that wasn’t worth replacing.  I found this out only after I had ordered a replacement bulb, waited for it to be shipped across several international borders in the middle of a pandemic, swapped the bulbs with no change in the output of light, and taken the projector to the local home electronics store, the owner of which told me the sad truth a week later.

In a time when Netflix is breaking its streaming records by the day, we were sitting in the dark.  In those six weeks, we watched one show on the screen that I use in the office, but that wasn’t exactly a cinematic experience, and we quickly agreed that it wasn't worth our time.  We sat out the lockdown without visual entertainment.  Now that the lockdown is over, the lights are back on.  And I have less time than ever to post.

Otherwise I would have written earlier that the consultation in Zurich was comforting, though it didn’t change the situation.  The specialist was as pessimistic as the doctors in Baden, but maybe slightly less blunt about it.  He talked about possible therapies as having the potential to make a difference.  He also rejected all of the suggestions I had come up with over the last few weeks.  Fasting:  Too dangerous, unlikely to help.  Trifluridine:  Overvalued.  T cell therapy:  Unlikely to work with colon cancer the way they’re currently done.  EGFR antibodies:  You’re better off with VEGF antibodies.  In any case, 5-fluorouracil does the main work during chemotherapy.  Changing the antibody won’t flip a therapy from failure to success.

He said all this with compassion and a quiet authority that left us none the wiser but oddly reassured.  I know things ain’t over until they’re over, and I’m ready to continue the fight.  I’ve started on the trametes extract and will try to do the fasting during the next chemo program.  The doctor in Zurich might not think much of it, but it’s a trick to pull, and I don’t have many left.

Wednesday, May 13, 2020

Free to eat

Today was not nearly as bad as yesterday.  It’s amazing how well one can endure several days of fasting,  Today, I felt stronger than yesterday and was more lucid.  My legs hurt a bit, as if my body was chopping down the protein in muscles to use as energy, but I achieved more during a day of home office than the previous day.  It was the third day without any calories, but I wasn’t hungry.  I frequently thought of food, though.

For lunch, I went for a walk.  It took me to town and to a budget grocery store where I sometimes buy certain things.  They have good pralinés and tasty peanut flips.  I doubt anyone outside Germany or Switzerland knows what these are.  This time I bought a few bags of different nuts, to give me energy without too much sugar over the next few days.  The nuts were my downfall.  I broke my fast an hour early when I opened a bag of walnuts before picking the girl up from daycare.

I should have broken my fast afterwards.  That was the plan.  It probably doesn’t matter, and I don’t consider the exercise a failure.  Seventy hours, 71 hours, 72 hours, who is counting?  Dinner was a relief, a release from strict abstinence, a return to normality - but less of a pleasure than I had expected.  In spite of the nuts, my belly was unprepared for the feast.  It wondered about the bread, the cheese, the poke bowl, and the store-bought tiramisu later on.  I realized a bit late that I would need lots of liquid with the food.  Now, late at night, I’m fine and ready for ten days of normal eating.

Will I start my second chemo program in ten days?  This is not clear yet, though it would fit well.  It depends on what the doctors think is best.  I can’t start early enough.  Why wait and give the cancer time to grow and spread?  Maybe I shouldn’t worry.  If research is right, I’ve just done the equivalent of a chemo session by fasting for three days.

Tomorrow, Flucha and I will go to Zurich for a consultation with the visceral surgeon we saw at the beginning of this journey.  This was suggested by my oncologist.  I agreed, though I’m not sure what we’ll get out of it.  What can a surgeon contribute?  My oncologist told me another surgery was out of the question, with the cancer dispersed rather diffusely in the liver.  Maybe the surgeon in Zurich has another opinion or fresh ideas.

Here are some of the questions I will ask him:

  • Should I get an EGFR-inhibiting antibody instead of a different VEGF inhibitor?  The first chemo program was not really such a resounding success that its elements should be retained.  The KRASG13D mutation that I have should allow working with an EGFR inhibitor.
    → The type of antibody is not going to change a therapy from failure to success (which makes me wonder why I’m getting a different anti-VEGF antibody).
  • Does my tumor overexpress VEGF?  This is apparently a thing.  It would explain the repeated use of the anti-VEGF antibody better than its effect, a general weakening of angiogenesis.
    → I didn't ask.
  • How about Trifluoridine?  I’ve seen this mentioned as an alternative to the 5-fluorouracil-based therapy I’ve received and am going to receive again.  It can only be good to change the therapy I’m receiving.
    → Highly regarded by some with little justification.
  • How about fasting during chemotherapy?  Does it make sense, and how to go about it - periodic fasting, caloric restriction or a ketogenic diet?
    → Fasting is dangerous (but I knew this already) and unlikely to be a panacea.
  • Are there any trials of CRISPR-based T cell therapy I could enlist in?  This is something I plan to read up on but haven’t yet.  Are other experimental therapies available?  I’m ready to try anything.
    → This has been shown to work in blood cancers and is not relevant for me at its current state.

The consultation tomorrow is at a quarter past eleven.  By 12, we should be back out of the hospital, a good time to go for lunch somewhere in a recently reopened restaurant in Zurich still reeling from the lock-down and avoided by fearful patrons.  I’m not afraid.  I’m looking forward to eating out for the first time in many months.  Plus, I need calories to rebuild what I’ve lost over the last three days.

Tuesday, May 12, 2020

Day two

I didn’t ride the trainer tonight, even though Tuesday is the day for it.  It’s not that I’m lazy.  It’s also not that I’ve ridden through the woods this afternoon.  I didn’t even ride to work.  I stayed at home all day.  The reason I don’t feel like exercise is that I haven’t eaten in 48 hours.  I’m not at my best, and too weak for exercise.

I didn’t have many expectations when I started fasting after dinner on Sunday.  I thought I’d be hungry, but that’s the only thing that hasn’t happened yet.  I guess the body turns down sugar consumption overnight.  If you don’t restart it with breakfast, the body remains in this state, somewhere between a snooze and hibernation, and doesn’t yearn for glucose.

The first day was surprisingly easy.  I wasn’t hungry at all.  A few cups of tea and a few bottles of water got me through the workday.  I felt fine and worked normally.  This didn’t seem bad at all, which makes sense because periodic fasting is well established as being good.  It shifts energy from proliferation to maintenance.  Normal cellular processes are slowed down or stopped.  Only recycling and repair are upregulated to extend survival.

I found three clinical trials in the US designed to assess the effects of fasting during chemotherapy (NCT00936364, NCT01175837 and NCT01304251).  Two of them have recently completed, but I didn’t find any results.  Instead I found another opinion piece, this time in Nature Reviews Cancer, that praises the potential benefits of fasting, published almost back to back with a response that warned of malnutrition and weight loss (and a riposte to that).  Malnutrition is not an issue for me.  I’m eating well.  Instead of losing weight, I gained a few kilograms during chemotherapy.  Now I’m down by more than two kilos.  This is quite a bit and urges for caution, but I don’t see this as a huge issue.  My appetite is strong, and I’ll regain the weight quickly.

The second day was much worse than the first.  I was still not hungry, but I felt out of energy, quite literally half the man I used to be.  I had urges to stuff my face with chocolate during the afternoon and with fresh bread at night.  I had no idea there were so many tasty things in the house.  They remained off limits to me.– I’m also very cold.  My body seems to have more important things to do than keeping me warm.

When Muslims fast during Ramadan, they frequently describe how their brain is more alert than usually.  They’re much more focused on the things that matter.  This might be true for me as well, but the thing that matters is food.  As the afternoon progressed today, I found myself increasingly obsessed with food.  It became the only thing I was thinking about.  Now it’s almost time to go to bed, and I still haven’t eaten.

Tomorrow will be my third day of fasting.  The cancer cells are hopefully exploding out of frustration at the lack of energy.  This picture gives me the strength to carry on, but I’m definitely looking forward to dinner.  I will probably stick to bread and cheese and take it easy at first.  No chocolate, no drinks, just clean living for the rest of the night.  Asceticism is definitely not my thing, but extraordinary situations call for extraordinary measures.

Sunday, May 10, 2020

Starving the cancer

I’ve now managed to read the review I mentioned in the previous post.  As I said, this is about the benefits of restricting various nutrients during cancer therapy.  The authors acknowledge periodic fasting (as outlined in the previous post) but think it’s of little use because cancer patients are often frail and won’t withstand the rigors of fasting.  An obvious alternative, periodic low-calorie and low-protein feeding results in a similar anti-cancer effect to that of prolonged fasting.  This caloric restriction has been popularized as the best way of extending one’s life span.  It is apparently easier to comply with and does less damage to a patient’s fitness than fasting.

Even caloric restriction has negative aspects.  Weight loss results if one consistently consumes fewer calories than one expends.  This is not a problem with periodic fasting.  The longer periods of feasting usually restore the patient’s body weight, much as the time off between chemotherapy sessions usually restores a patient’s blood cells and good spirits.  In contrast, a protracted caloric deficit might render a patient weak and maybe even incapacitated.

How about just restricting the amount of glucose in one’s diet?  Glucose is a critical nutrient that enters various metabolic pathways.  Tumors need it at high levels to support their growth.  Avoiding carbohydrates and following a so-called ketogenic diet would achieve that.  The keto diet doesn’t work for people with mutations in the PI3K pathway, which mediates glucose-driving signalling.  In cancers where this pathway is constitutively active, the amount of glucose makes little difference.  I don’t have mutations in this pathway.  Maybe I could go keto.  As chance has it, Flucha tried this for a week or so not too long ago.  She cooked a few interesting meals that turned out surprisingly tasty.

Among the three options, periodic fasting sounds the most sensible.  It is the simplest but has the most serious impact on your metabolism.  Instead of restricting this or that nutrient, you restrict them all.  To fight cancer, it makes sense to use the biggest guns in the arsenal.  I think I’m strong enough to go without food for a few days.  To find out how it feels – without having to deal with chemotherapy at the same time – I will fast over the next three days.  I had my last meal this evening at 7 pm.  I’ll eat again on Wednesday night.  Let’s see how I fare until then.

Saturday, May 9, 2020

Food and cancer

A recent article in Cell showed that broccoli and related vegetables such as cauliflower and cabbage contain chemicals called glucosinolates that bacteria in the human gut turn into isothiocyanates, compounds with protective effects against certain cancers.  That’s of no use to me obviously.  I already have cancer, despite having been a happy eater of broccoli for ages.  Maybe I lack the bacterium whose enzymes perform the chemical reaction.  It’s called Bacteroides thetaiotaomicron, and if you have a hard time reading the name, here’s the Greek version: θιο.  That’s more like it.

If there are foods that help prevent cancer – and there are many more besides cabbage and broccoli – maybe there are also foods or supplements that help the body fight cancer.  They could boost the body’s immune response, augment the effect of chemotherapy, or be directly toxic to cancer cells.  Polysaccharide K (PSK), derived from the mushroom Trametes versicolor, is such an example.  It’s been used to supplement chemotherapy in Japan for many years.  Clinical trials have shown improved survival and slower disease progression in patients.  PSK is not available in Switzerland, but I have now purchased two tubs of Trametes capsules and will start self-supplementing.  I don’t expect it to help, but it’s unlikely to hurt.  Even if it does hurt, I’m in such a bad place that it won’t matter.

For something more scientific than a poorly regulated supplement, I obtained a review with the enticing title Dietary modifications for enhanced cancer therapy, which appeared in Nature a few weeks ago.  My expectations were high, but the review did not contain any silver bullets.  No word of polysaccharide K or other polyglycans from magic mushrooms.  In fact, it's not about supplements at all.  The article focuses on the omission of various nutrients.  Trained in the study of scientific literature, I skipped straight to the discussion after reading the somewhat vacuous abstract.  The authors conclude that “there are still no clear guidelines or recommended regimes of dietary modification for patients with cancer.”  I could have stopped right there and drowned my pain in another glass of red wine – wasn’t that considered the recipe for a long and healthy life at some point? – but I wanted to know a bit more.

Towards the beginning of my first chemotherapy program, when I recovered from surgery and my doctors talked about retaining or even gaining weight, a friend of mine had mentioned fasting as a strategy proposed by Russian scientists that no one in the West is aware of.  It seems someone is aware after all, because the review in Nature states that “the combination of prolonged fasting cycles (48-60 h) and chemotherapy significantly improved the response to therapy in mouse xenograft models of breast cancer, melanoma, glioma and neuroblastoma.”  Now that’s mice and not humans and a bunch of cancer models that are not colon cancer, but it’s interesting anyway.

The original publication (not written by Russians) even claims that “cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs”.  That’s a strong statement and worthwhile to consider in its entirety.  From the first half you might ask why bother with chemotherapy if fasting is as effective.  Surely it is cheaper and has fewer side effects.  Is the evil pharmaceutical industry talking us into something we don’t need?  The second half tells us that starvation might potentiate the effects of chemotherapy, which is quite something.

Why might periodic starvation be good?  Fasting induces healthy cells to reallocate energy towards maintenance pathways at the expense of reproduction and growth.  Chemotherapy targets reproduction and growth.  In fasting patients, cancer cells, which can’t activate the same stress resistance, bear the full brunt of chemotherapy.  In addition, starved cancer cells might try to compensate for the lack of nutrients by increasing translation, which consumes even more energy and might promote oxidative stress, DNA damage and eventually cell death.

What might this look like in practice?  Patients fast for two to three days before chemotherapy and for 24 hours afterwards.  This means no food at all, only water.  The paper claims that this is well tolerated and might also reduce side effects because healthy cells become resistant to the drugs.  The mice in the study regained their weight after five days of feasting.  I don’t know how I might function under these conditions.  Could I still work?  What about exercise?  I’ve never tried anything like this, but at this point, it seems worth a shot – or at least a discussion during the consultation at the University Hospital in Zurich next week.

But maybe it’s all for nothing?  The article suggests that fasting after chemotherapy is important to protect healthy cells.  To minimize toxicity when refeeding begins, the duration of fasting should be proportional to the half-life of the drug.  Here I see a serious problem.  My chemotherapy takes 48 hours.  I cannot possibly fast 48 hours before chemotherapy, 48 hours during chemotherapy and then another 24 hours after chemotherapy.  That would be five whole days.  I wonder what the doctor will say.

Now I didn’t even get to read the review that triggered this post.  Something for another time.

Wednesday, May 6, 2020

Hard to believe

I’ve lived the last few days in a bit of a daze.  The meaning of the PET-CT result is sinking in.  My flight has been called.  The final departure is not far off.  My defenses are wearing thin.  I don’t exactly know where I will find additional strength for another fight.  Surgery is not an option, said the oncologist.  Chemotherapy doesn’t seem to cut it.  My cancer is stronger than what they injected in me, and all they can think of is doing it again.  It’s a terrifying prospect.

I try to keep up appearances.  During the day, I try to go about my normal business, which works better when I go to the office.  At home, motivation for work or anything else is hard to come by.  At night, it gets worse.  I’ve not ridden the trainer in a while.  I sit in front of various screens not doing anything.  The papers I’ve talked about in the previous post remain unread.  This is not the post about KRASG13D.  Time passes.  My mind wanders, but it never gets anywhere comfortable.

The whole story from its beginning with a bang in September until its most recent reversal of fortune is hard to believe.  I was a healthy man with few bad habits.  Up until the fatal diagnosis, I had no inkling that anything was seriously wrong.  No way that I could have caught this earlier to fight with better odds.

I’m still in good shape.  Today I rode my bicycle up the hill between home and work, temporarily getting lost on the ridge when the only trails I could find were steep chutes that my bike was entirely unsuited for.  I attempted one but had to turn around when my skinny tires, despite drawing deep cuts into the mud, just started sliding.  I look like I always do, even though I’m ravaged inside.  I haven’t lost any weight.  For someone who doesn’t know, it would be hard to believe how rotten I am.

It’s funny, in a morbid way, how hard to believe this year has been so far.  Who would have thought that we’d be suffering under a virus, with social life and city life suspended, shops, restaurants and parks closed, old folks locked up like lepers, and people dying by the thousands from an illness no one had heard of half a year ago.

Banned from work because of corona, Flucha has used the last few weeks to declutter our house.  Everything that didn’t have an immediate use was put on an auction site.  I expected most things to sit there idly, but lots of people must feel a deprivation from shopping that they’re trying to overwhelm in the strangest ways.  Hoarding loo roll is one example.  Another is madness in auctions.

Last year, I bought speakers off a colleague of mine.  My old ones remained in the basement, a fate they know from when I lived in the US.  They never left Europe, preferring to hibernate at my mom’s.  Flucha put the speakers online with no description beyond “speakers”.  Hours later, someone had chosen not to bid but buy them now, and transferred 50 francs.  I had paid around 300 francs a quarter century ago.  When the guy picked up the speakers, he lifted them, said, “They’re solid.”, smiled, and walked off a happy man.

When I finally decided on a new CD player and amp, my old set, purchased together with the recently sold speakers, went up for auction.  I had no say and nothing to do.  Flucha culled a description from the internet, and a few days later, the CD player was replaced by a crisp green 50-franc-note.  Again, who buys 25-year-old kit for such prices?  It’s not that we’re selling vintage.  This was entry-level stuff back then.  The amp is still mine but someone has bid on it.  The buy-it-now can’t be far off, though it’s hard to believe.

Today I got a call from the University Hospital in Zurich.  I’m having a consultation with the doctor who gave me a second opinion before the first chemotherapy program started.  He agreed with everything the doctors in Baden had done and said.  HIPEC would not have been sensible, he said.  Would it have made a difference?  No one will ever know.  I’m not sure what to expect from him.

He will surely agree that another chemo is the way forward, suck it up and suffer through it.  With some luck, you’ll still be alive when it ends.  But will he have any unexpected insights?  Will he recommend experimental therapies that might help?  Will he know of clinical trials I could enlist in?  It’s hard to believe, but a lot of hard-to-believe things have happened this year.  Hope dies last.

Sunday, May 3, 2020

Taking charge

It would be fair to say that my body failed me.  Despite the reasonably good care I took of it and without any familial predisposition, it let a few cells loose, letting them proliferate in my gut and then, when this had reached its limit, run wild inside me.  Now it’s out of control.  This sounds like the beginning of an exciting story, but without people, no one will read it.

It would be unfair to say that my doctors failed me, but that’s certainly one way of looking at it.  They failed to treat my disease successfully.  But maybe it wasn’t them.  Maybe blame has to go to chemotherapy, which didn’t manage to stop the growth of the rogue cells inside me.  Again, this is an abstract concept that’s not going to make a good story.  I could take a few steps back and say the scientists in pharmaceutical companies failed me because they haven’t come up with a therapy that’s efficacious against my particular cancer.

There are many ways of attributing blame.  None of them does me any good.  It’s much better to mobilize the scientific education I enjoyed and dig into the literature to see if there’s anything that might be of use to me, anything that might be done differently to avoid having to expect a different result with the same approach.  This is not an idea that has recently come to me.  Over the last six months, I have downloaded a few dozen papers with intriguing titles, but outside the reports on clinical studies of the effect of polysaccharide K, I haven’t read any.  This is now changing.

By utter chance, I noticed a paper about “A systems mechanism for KRAS mutant allele-specific responses to targeted therapy”.  I do have a mutation in KRAS.  Targeted therapy surely sounds better than hitting the body with a broadly acting inhibitor of RNA and DNA synthesis, such as 5-fluorouracil.

The abstract was even better than the title:

“Agents inhibiting the epidermal growth factor receptor (EGFR) benefit many colorectal cancer (CRC) patients, with the general exception of those whose tumor includes a KRAS mutation.”

Consistent with my KRAS mutation, I received antibodies against vascular endothelial growth factor (VEGF) and not EGFR.  This is also planned for the second chemo run.  However, the abstract continues,

“among the various KRAS mutations, that which encodes the G13D mutant protein (KRASG13D) behaves differently; for unknown reasons, KRASG13D CRC patients benefit from the EGFR-blocking antibody cetuximab.”

I do have the G13D mutation.

Why am I not getting cetuximab?  This is a question for my doctor.  It might not be approved for use in my case, and the original clinical trial (ten years old by now) showed a depressingly small effect, but it’s worth a try.  At this point, anything is worth a try.

The question for another post is what KRAS is, why KRASG13D behaves differently from wild type and the other oncogenic mutations, and why it would be susceptible to EGFR inhibition in contrast to any of the other mutations.  I’m bailing out here because it’s late, the post is already long enough, and I’m not sure anyone would want to read what will follow.

The next post will be scientific, a journal club if you will, demonstrating my understanding of what goes on with KRAS and why.  This is my fate.  I need to know the background.  So far, I’ve given cancer papers a wide berth, but this can’t be justified anymore.  I need to take my health into my own hands, at least the theoretical aspect.  Bear with me.

Friday, May 1, 2020

Madness

Doing the same thing over and over again and expecting a different outcome is a sure sign of madness.  Repeating almost the same chemotherapy on a cancer that has shown refractory to it seems to me to fall into the same category.  Still, what can I do?  Doing nothing is not an option.  It won’t give better results – which might now need to be measured in months or years and not survivorship or not.  Jumping off a bridge is not an option either.  I would be throwing away too much.

The clinical study that adds methadone to chemotherapy to see whether it improves the outcome is close to enrolling patients.  The hospital is in Ulm, just a few hours from here.  There’s a handy questionnaire on the website to check whether one qualifies.  I don’t.  I have apparently not exhausted all the options of chemotherapy yet.

This is bad, but it could also be a reason for hope.  In my upcoming (though as of yet still unconfirmed) second chemotherapy program one of the drugs (oxaliplatin) will be replaced by another (irinotecan).  To both deserve a box in the questionnaire, they must be sufficiently different from one another to maybe make a difference in the therapy.  Maybe I’m not about to repeat what I’ve already done.  The bad news is that the study works with the mix containing oxaliplatin, against which I had an allergic reaction such that it was withheld during the last session.  Any positive outcome might not apply to me.

Another compound on the list is trifluridin, a nucleoside analog that I haven’t encountered yet.  It was never mentioned as a possibility, but I see that it’s available in Switzerland and prescribed in cases where chemotherapies with oxaliplatin and irinotecan have failed. It seems that there are even bleaker cases than mine, and that I have quite a way to go before giving up becomes the only way out.

This should lift me up, but it’s heavy lifting.  Since the devastating news from the oncologist yesterday, I haven’t exactly been bouncing around with joy.  With the futile mental acrobatics of an empty head, I’ve almost managed to persuade myself of the utter despair of the situation.  I spent a fortune on a new stereo that arrived this morning, but what’s the point?  Who’s going to appreciate it?

Everyone knows they’re mortal, but the certainty is a distant one, and it’s easy, almost instinctive, to ignore it.  If the inevitability of death becomes imminent, it has a different effect.  It colors all thoughts, blunts sensations and subdues energy and enthusiasm.  Why bother becomes a logical reply to almost anything.  Once you’re in this hole, it’s probably very difficult to get out.

I was standing at the edge of the hole a few times today.  It was hard to focus on work, and during the bike ride in the morning (as if I were a graduate student again), the road was struggling to hold my attention.  Questions that one shouldn’t have to ask kept popping up in my head.  Are the children going to be ok?  They're so little – and so good.  It’s my duty to send them off into their own lives.  This is difficult when they’re only 3 and 5.  How will Flucha cope?  Why am I being deprived of forty years of my life?  All good questions and all utterly pointless.  Even if anyone had good answers, it wouldn’t do me any good to know them.

In the end, I cut the nonsense.  There’s more to life than thinking about its end.  I finished my work for the day and went down to connect the stereo.  An hour later, with the amplifier warmed up, I enjoyed Saint-Saëns almost as if I were sitting in a concert hall.  At least that’s what I’m trying to convince myself of.  It helps justifying the expense.  I sit on the sofa, the children run around and scream, Flucha cooks burgers, and I imagine the next steps.  It would be madness to stop fighting.