Life in a Clinical Trial: The Worm's Eye View

Now that I've versed you a bit on the big picture, it's time to share clinical trial life in the form of the little picture: that is, moi.

Immunotherapies work differently than chemotherapies. The latter just doses you with toxic chemicals that have been shown to do a reasonably good job at killing cancer cells without killing so many healthy cells that it, well, kills you. The former helps your immune system to do its job better. For instance, the durvalumab that I take is a PD-L1 inhibitor. My understanding (and anyone who is qualified to correct me or add additional info, please do!) is that this drug stops the body ("inhibits" it, get it?) from making the kind of protein (PD-L1) that some cancer cells smear all over themselves in order to hide in plain sight. So if my cancer cells were producing a lot of PD-L1 - well, they aren't anymore. And instead, as I mentioned in the last post, the cancer cell is naked and being pointed out and laughed at. The second drug I take is called a checkpoint inhibitor, and it helps both NK cells and T cells do their work of demolishing cancer cells better. The science behind it is particularly dense, but the most simplified version, as I understand it, is this: pretend that a cell needs to dock to another cell in order to help repair it, and so cells offer up little docking stations of various kinds that allow the NK or T cells, which are both built to fix (or destroy) cells that need it, to come aboard. Those docking stations give the fixer cells info about what's wrong in the cell, and then the fixer cell says, "Ah-yup" and repairs the cell or blasts it to smithereens, and then goes about its business. Now, many sneaky little cancer cells send up "false flag" docking stations, and the NK or T cell docks up - but it can't unload or find anything wrong because it can't get any real information out of the cell...because the cancer cell sent a fake!! They really are sneaky little bastards. Anyway, to get back to the checkpoint inhibitor I'm taking, it basically helps block the fixer cells' ability to hook up with fake docks. And so the cells will hook up to the actual docking stations instead and do the jobs they're made to do. Ta-da! 

It's great in theory, and so far, it's working to stabilize my disease. Good job, immunotherapy drugs! They really are amazing inventions - and understanding even a little bit about how they work shows you just how difficult it is to "cure cancer." Each cancer works differently from every other cancer, and even within a cancer type, there are a number of subsets and types of disease. So, cancer cells work in very different ways, throw up a wide variety and kinds of different defenses...and most cancers will evolve over time. Terribly complicated business, trying to rid the body of cancer cells once they've arrived.

Just because the drugs are immunotherapy drugs, it doesn't mean that they have no side effects. Although they're designed to help the immune system attack more efficiently, they're still drugs and can be toxic and create all kinds of problems. The biggest concern with immunotherapies generally is that they could push the immune system to work overtime, and the immune system will then start attacking healthy cells and systems, creating auto-immune crises - or as one member of my medical team said, "anything with an -itis." Within my particular trial, the medical team is on the look out for a suddenly overactive or underactive thyroid; for a pancreas that quits working well; for a liver that suddenly gives evidence that it's under attack; for lungs that acquire pneumonia-like symptoms without any pneumonias around (that's called "pneumonitis" and I've already had it once, likely as a result of SBRT to my lungs). This is why they do so much bloodwork, see: they're looking for evidence that any of the above organs, and a host of other systems and organs, are suddenly going off the rails. There are also fevers, which happen a lot when your immune system is fighting hard (think about your last bad cold or flu), and fatigue (again, your body is redirecting its energy to the fight at hand, and just gives you the leftovers to go about your day), and cold-like symptoms (very common side effect with immunotherapies!). There are lots of other side effects, too - headaches, dry skin, joint pain...the list is long, so I'm just highlighting some of the most likely ones.

For me personally, one of the drugs seems to give me a bit of a fever (around 100) that begins a few days after the infusion and sticks around for a couple of days, although that didn't happen last time I received it. I've also had a fair amount of nausea (which is not fun at all), lots of headaches, and a variety of lung problems - low oxygen, congestion, wheezing. This bit may just be a coincidence due to an absolutely terrible spring cold and allergy season here, or it may not. Same with the fevers, headaches, and so on, really. That's the thing: it's harder to tell whether your symptoms are drug induced or just nature induced with immunotherapies. So far, I've had to get several x-rays and emergency CT scans to look for possible signs of pneumonitis (don't have it! Yay!) due to breathing problems. And I've been pretty tired - I sleep at least 9 or 10 hours a day, which is totally crazy - although I'm not NEARLY as tired as chemo made me. At its worst, chemo creates a bone-deep, permanent feeling of weariness. You wake up in the morning, crack your eyes open, and wonder when you'll be able to summon the energy to get up. Then once you're up and dressed, if you even make it that far, you're ready to crawl back into your bed (and I, for one, often did). At best, chemo leaves you feeling like if you could only get the perfect nap in, you might be able to function (sort of like that tired you feel after a good long night of proper drinking - BUT WITHOUT THE DRINKING) pretty well. But all the naps in the world don't really make it go away, and so you make do and silently curse people who tell you that you look like you're not feeling well.  At least now, I have already enjoyed a number of really good days, where once I'm up and running, I actually get things done and make it through the day! I've been blogging and going to yoga and working out at the gym sometimes. I read books! I made dinner last night, for Heaven's sake. AND I made cookies! What?! This sounds really pedestrian to most people, I know, but for me, it's amazing. And here's the real kicker: I didn't even realize I'd felt so poorly because I'd been taking chemo for so long, I couldn't remember what feeling "good" actually meant. Even after I stopped (my last chemo dose was  1/5/2017, in preparation for the trial), it wasn't until the last six weeks or so that I even started to feel truly energized and alert on good days. Even better, my chemo brain fog is finally lifting! Wow!

Me, contemplating getting out of bed.

Now, the lung problems may really just be a result of the inflammation that naturally occurs when you're fighting off a virus (or a disease) - but because my lungs are already compromised, the reaction is somewhat magnified. The short version of how and why they're compromised goes sort of like this. I have multiple lung tumors (five that we consistently see on scans) on both lungs from my cancer. The largest is about the size of a golf ball and lives in the lower lobe of my right lung. I have decided to name him Birdie, in keeping with the golf theme. In addition, I suffered pneumonitis several years ago, likely as a result of SBRT, which scarred my right lung a little bit. I also have some minimal scarring from the removal of lung tumors via SBRT in 2014. There appears to be permanent pleural effusion that has set up camp in my right lung.  Beginning in the late fall/early winter of 2014, I discovered that I had two broken ribs on my right side. These, too, were likely from the aforementioned SBRT effort (and thus we don't use SBRT on my lungs anymore, see?). That injury ended up sort of snowballing, and by the middle of 2015, I had four broken ribs at once, and all in a row. The good news about that ongoing fiasco is that: one, there aren't any ribs left to break, really, except the bottom two and they're small potatoes (it's the big ones that will really get you), and two, although broken ribs don't really "heal," per se, they have finally, after two years, settled down enough for me to be back on my yoga mat (YAY! Hearts and flowers and rainbows and butterflies YAY!), although I do despair of every being able to do crow, side crow, or a proper backbend again. If I even try, I can feel the whole right side of my body tapping me rather fiercely on the shoulder.  But let's not dwell on that. The only other weird thing with my lungs is that sometimes one collapses a bit and then fluffs back up. It also doesn't help that I've never had terrific lung capacity and that I am allergic to just about everything outside (and some stuff inside, too).

Even before I started this trial, then, you can see why I had to use supplemental oxygen from time to time. On a good day, my oxygen saturation levels are around 93 (healthy lungs usually are around 97) and I can function on my own. But if anything is "off" - a cold, allergies, forest fire (particulate in the air), being at altitude, and so on - my O2 levels sink below 90, and that's when you need supplemental oxygen. I used it often enough that we bought my own concentrator (his name is O2D2 and he fits in a special backpack and only weighs about 10 pounds, which might sound like a lot but its hella lot better than those massive metal canisters that my insurance covers, which make me look and feel like a sad, deranged clown).  Since the trial began, I've had to use oxygen MUCH more frequently - so much so that we bought (with the help of my mom - Thanks, Mom!) another, even smaller oxygen concentrator (her name is, according to her sneaky nature, Double O. No need for a 7, thankyouverymuch, and she only weighs 3 pounds!) so that I can  run errands or exercise and so on without breaking a sweat or feeling conspicuous. Why is this happening? No one knows for sure, but I'm betting that just the inflammation that naturally occurs when your body is fighting something has been enough to upset my formerly consistent O2 levels. So, oxygen. It drives me crazy and I get tangled in the cannula (especially when I'm sleeping! Argh!), but I'll take it. What choice do I have, really?

So, all things considered, I'm doing pretty well on the clinical trial thus far. My first scans showed zero growth of my existing tumors, I'm feeling sort of human again, and (added bonus) my hair and nails are finally growing again at a decent rate. Side effects abound, but I'm used to those. And I have some new outlooks and plans for the future that I will share with you soon!