When Francis Bacon said the remedy is worse than the disease, he wasn’t thinking of metastatic tongue cancer, where both disease and remedy are horrific in their own nightmarishly unique ways. Right now I’m facing a related dilemma, in that my cancer is aggressive and incurable, but the clinical-trial drug I’m taking is producing side effects that may themselves be deadly. Cancer treatment is of course violent: my tongue was cut out, my tissues burnt with radiation, my veins infused with both well-tested and experimental poisons. Cancer is violent too; the headaches I had before treatment left me with a foot in my own grave on May 24, 2023, the night Bess and I got married, and the night before the total glossectomy. We both knew I might not wake up from the surgery.

Despite the pain and the fatigue and the overall struggle, the choice to endure—to spend time with Bess, and writing, and trying to squeeze what I can out of life—has, well, endured. “Endure” means “enroll in clinical trials,” since the only existing treatments are palliative chemotherapy followed by death. When I was on petosemtamab / MCLA-158, the first clinical-trial drug, I endured full-body skin rashes and “paronychias” (infections and inflammation around the cuticles of the fingers and toes) that made it hard to type and walk. I bled a lot. When petosemtamab stopped working on Mar. 13, Bess and I scrambled madly, and I survived long enough to enroll in the Seagen PDL1V trial. I had high hopes that PDL1V would come with fewer side effects.

PDL1V is an antibody-drug conjugate (ADC), which, according to Seagen, means that the drug “specifically target[s] certain proteins that are found on the surface of tumor cells.” ADCs “recognize and bind tightly to targets expressed in tumors, while limiting binding to normal tissues.” Conventional systemic chemo causes numerous side effects because the chemo hits not only the cancer cells, but also all the other rapidly dividing cells in the body. ADCs are supposed to ameliorate that problem. PDL1V delivers a gnarly chemo agent called MMAE, which Wikipedia says “show[s] potency of up to 200 times that of vinblastine, another antimitotic drug.” I don’t fully understand what that means, although Bess says it basically has to do with a drug’s effects at a certain concentration, meaning that 1mL of MMAE is as powerful as 200mL of vinblastine. It does make MMAE sound like it’ll do bad things to tumors.

The question is, exactly how targeted is PDL1V? While I had fewer side effects from petosemtamab than the average patient, I appear to be on the other end of the curve for PDL1V—meaning it’s targeting the tumor, but it also seems to be targeting parts of me that aren’t tumor, too.

My first PDL1V dose was April 15, and I got through that week okay. Exhaustion and difficulty eating were the most prominent side effects. The second dose was April 22, and, like many ominous problems, the ones from that dose snuck up on me: by Tuesday April 23, I was feeling lightheaded, weak, confused, and generally out of sorts, which isn’t entirely unexpected when starting a new, experimental anti-cancer regimen. I’d seen the PDL1V side-effect list, too—fatigue, nausea, constipation, diarrhea, decreased appetite—a generic list of symptoms, and yet mine were consistent with them. Practically every medication carries a list of similar potential side effects, maybe because a lot of people are tired and have GI problems. Although I knew by Apr. 23 I was doing poorly and not eating enough (which is maybe not surprising given that I was sleeping or dozing for twelve hours a day), I checked my weight and discovered that I’d plunged from ~144 lbs down into the 133 – 136 lbs range. Crisis. It’s possible to starve to death by accident, since I’m never hungry and have to force myself to consume every calorie. But getting close to starvation will interrupt treatment, which is also deleterious. The world is full of perils, and Bess and I are navigating the cancer ones as best we can. If you’re reading this and wondering why a dip in my weight caused alarm bells, it’s because a series of seemingly tiny, benign problems can turn out to herald a crisis. I used to be robust, but now I’m fragile, and fragility demands diligence if I’m not to slip into the void.

In cancer therapy for an incurable malady like mine, there’s no promised land short of an extremely improbable, though not impossible, “complete response”—or permanent remission—but there are temporary safe harbors in which one can float for a time between dangerous ocean sojourns. Petosemtamab was such a relief. Sometimes what appears to be a safe harbor turns out to be infested with unexpected challenges, much as another may turn out to be too shallow, or controlled by pirates, or full. Last month I wrote seven thousand words about the epic journey from the MCLA-158 / petosemtamab clinical trial that kept my tumors checked from Sept. 2023 to March 2023, in “The emotional trial of clinical trials: It’s like online dating except if you choose wrong you die” and “The clinical trial trials: death by a thousand cuts.” It’s like The Lord of the Rings, except that the wizards and high elves are drug researchers, the men of Númenor are oncologists, and I’m basically a hobbit, sustained to a degree by courage and fortitude but fundamentally buffeted by forces frustratingly beyond my control.

If you read mountaineering disaster stories like Jon Krakauer’s Into Thin Air, there’s almost always a pattern: under-preparation; inexperienced climbers; failure to fully understand and incorporate how rapidly weather can change at altitude; and, perhaps most importantly, not turning back the minute the weather is changing for the worse. “Under-preparation” and “failure to recognize the truth of the situation” is probably a good, simplified version, and that happened to me: I wasn’t adequately prepared with GI meds like Zofran, Imodium, Bentyl, Simethecone, and even basic Pepto-Bismol. Even worse, on Apr. 23 I didn’t recognize what was happening to me, but Bess identified dehydration as a potential cause. Diarrhea causes dehydration and that in turn causes weight loss. Bess scolded me for not telling her of my GI symptoms sooner so that she could play doctor for me. Then again, is it playing doctor if she is a doctor?

By Apr. 24, two days after the second PDL1V treatment, dehydration became a focus of our efforts. In many if not most cities, a bunch of IV hydration companies have sprung up to cater to the hungover and coming-down-from-drugs crowd, and we live in prime territory for those clinics because numerous alcohol-dispensing points are nearby. Bess and I inadvertently moved into an area called “Old Town Scottsdale,” which is known for its bars and parties; you may read “inadvertently” and think: “How does one ‘inadvertently’ move somewhere? That seems like a pretty deliberate act.” While the moving itself was advertent, we left New York in 2020 during COVID and I picked our apartment based on its (relative) walkability, it being within acceptable range of Bess’s work, and the number of coffee shops within easy biking distance. I didn’t think to check for nearby bars. Probably we should’ve moved to downtown Phoenix, but Bess’s impressions of downtown Phoenix were decades out of date, and she thought it only fit for seeing a concert or a play, then driving away as fast as possible, unless one wants to score meth or paid sex of dubious quality beneath the Van Buren underpass.

Anyway, we did what we did and mistakes were made, but living beside a bunch of IV hydration companies proved useful because one was a two-minute walk from our building. By Wednesday, Apr. 24, I was being rehydrated, like a desiccated plant. Although IV bags through the IV clinic aren’t cheap—$100 for one liter, $150 for two—they’re much, much cheaper and more convenient than emergency rooms, which is where I was headed. My weight was low, my hold on consciousness becoming more tenuous, my heartrate up and erratic, while my blood pressure was down, and alleviating those problems was well worth the cash.

Unfortunately, I kept experiencing what we’ll call GI distress, which included feeling like my guts were being stirred with a hook every time I ate. The first round of PDL1V on Apr. 15 had caused exhaustion from the night of Apr. 17 until at least Sunday Apr. 21, but it didn’t cause a ton of GI issues, so those caught Bess and me off guard. The second round brought more fatigue, along with persistent GI struggles.

On top of the GI issues, we did get the go-ahead for spot radiation from Seagen / Pfizer, via START-Utah, the organization that is hosting the PDL1V study. So on Apr. 24 I got the two liters of IV fluids and my first session of spot radiation. The spot radiation immediately caused my neck to tighten, my voice to become hoarser and raspier, and my ability to swallow to be impaired. Bess and others point out to me, too, that radiation is commonly exhausting even for people not getting chemo-like agents. Still, I think the PDL1V accounts for the majority of the exhaustion, though I can’t rule out some contribution from radiation. When I got extensive radiation from Dec. 2022 – Jan. 2023, though, I remember the first three weeks of it not being bad in terms of side effects, and then the side effects getting worse by the day after that. But I wasn’t on any chemo agents from Dec. 2022 – Jan. 2023. I was, of course, also in much better physical shape then, and now I often seem a bit like a shambling reanimated corpse whose parts do not fit or act together all that well any more.

There’s also some evidence that MMAE in particular radiosensitizes tumors, and so we may have gotten some synergistic chemo-radiation effects. I feared, however, that the treatment might shrink the tumors and leave my neck fibrotic, and me unable to swallow semi-effectively, or speak. Then again, the tumors could grow and cause the same problems. Here we again see the remedy-disease conundrum.

Over the week of Apr. 22 – 29, the giant bulges on the left side of my neck have flattened out, which may imply PDL1V’s effectiveness. One site leaked a huge amount of goo reminiscent of the necrotized lymph node that startled me into an emergency ENT appointment back in November; Bess thinks the goo is necrotized tumor. The headaches that were plaguing me from the end of March through a lot of April were reduced in intensity, so it’s possible that the next CT scans will show PDL1V working well. It’s also possible that the radiation, potentiated by the drug, will make the PDL1V appear to have worked better than it would have on its own, even though I only finished two of my five spot radiation doses.

But the side effects and weight loss of the last two weeks make me doubtful PDL1V is sustainable. I spent most of Apr. 24 – 29 in bed. On Apr. 26, I foolishly drove myself to Mayo for a second radiation treatment while Bess was at work, when I should have taken an Uber because I could barely keep my eyes open. Eventually the GI problems petered out, but they were gross, and extensive, and even Imodium and related meds did not fully eliminate them. From Apr. 30 – May 5, I felt gradually better, but the absence of new material here on The Story’s Story gives a sense of how I was doing physically and mentally. I started writing this essay about PDL1V side effects on Apr. 26. It’s not like me to take two weeks to write an essay like this.

I got a third PDL1V dose on Monday, May 6, and now I’m armed with an army of medications to combat potential side effects: a dose of Aloxi (“super Zofran”—an anti-emetic) and 4mg of dexamethasone with the PDL1V itself. Lots of Imodium. Bentyl and Simethicone, for gut pain and cramping. Ativan at night. I think a couple of others I’m not remembering right now. The side effects have been better than they were after the second dose, but they’ve still been rough. Dr. Call, my oncologist at START-Utah, says that we can reduce the PDL1V dose in an attempt to cut back the side effects while likely retaining the anti-cancer properties.

There’s another possibility, too: right now we have a slot for an immunotherapy called BGB-A3055. Next week I’ll get CT scans to check and see what the PDL1V has done so far. If PDL1V has minimal anti-tumor effect, then leaving the PDL1V trial is easy. But what if it shrinks my tumor size by 30% or more, at the cost of me feeling abysmal for two weeks out of three, and barely being able to eat? How long can I keep this up, even with supportive medication?

The questions likely don’t have answers. I’m tired of being tired, after a mere three weeks of treatment. Most likely, we’ll get ambiguous results from the CT scans next week: tumors  that are, say, 15% smaller—which is great, but enough to endure the GI problems and exhaustion?

Cancer brings with it a whiff of medieval torture options: would you rather be placed on the rack or quartered? Either way you’re torn apart. Either way, a third option would be preferable, though there is only one to choose from: whether or not to endure the cure or the disease at all.

Bess is the main reason to persist. It’s dispiriting to have poured so much effort into finding PDL1V and getting into the trial, only to find myself on a ship that seems to have a serious hole in it, and some seaworthiness questions. Yet that’s part of the experimental-drug process.[1] We make choices based on incomplete information and do the best we can with those choices. I didn’t foresee being walloped by PDL1V GI side effects. I didn’t foresee either the sweaty, intense, month-long period from Mar. 13 to Apr. 15 when finding a clinical trial utterly consumed Bess and me. In early April, I wasn’t convinced I’d make it to the next trial. Yet I’m still here, despite having shed pounds that I didn’t and don’t have to shed. Surprises pile up. Some are pleasant: I didn’t think petosemtamab would work, or that I’d see 2024, and yet it did and we’re now well into 2024. I’ve gotten to spend a huge amount of bonus time with Bess.

For now, my choice remains to endure. The question, as I contemplate whether it’s better to persevere on PDL1V or transition into the next study is: will the new drug allow me to?

If you’ve gotten this far, consider the Go Fund Me that’s funding ongoing care.

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[1] At least I didn’t wind up in the trial of magrolimab, which doesn’t seem to be generally effective.