On March 23, 2023 my life was turned upside-down and inside-out by a brain cancer diagnosis. The kind of cancer I have, glioblastoma, is terminal. You don't "beat" this cancer, it kills you. But before it does that, it turns you into something you, your friends, and your family will not recognize and may only barely believe. This isn't a lump like a lot of cancers. It's not a mass of clearly defined tissue that can be cleanly carved out and chucked into a biohazard container. It's more like a spider web that spreads throughout the brain, commandeering the very pathways the brain itself established for maintenance. As glioblastoma spreads, it transforms healthy brain tissue into flakey, gooey mush. It leaves behind a complex mess of healthy, diseased, dying, and dead brain cells everywhere it goes. There is no way to repair the damage and no way to stop the spread.
And it's been like this for decades. Untold millions of dollars spent on research and tens of thousands of dead patients over the last two decades has barely moved the needle on quality or quantity of life. All anyone can do is hold the onslaught off for as long as possible. Twelve to eighteen months after diagnosis half of glioblastoma patients are dead.
I won't recount how this has affected me personally. For that, have a look at the archives.
But it's worth reviewing the treatments I underwent, and and those I didn't. Because what I'm going to talk about here is why I abandoned the "standard" treatment and exactly what I did instead.
In March I underwent brain surgery to remove the part of my tumor visible by MRI ("resection"). Actually, more than all of the MRI-visible tumor was removed. Not every resection is this successful, often because the tumor is too close to vital brain areas. But my tumor was centered in a relatively "quiet" part of the brain, the right parietal lobe. The term for this somewhat unusual procedure is "supermaximal resection."
Shortly after surgery, I underwent chemoradiotherapy, as per the standard of care. In this procedure my brain was irradiated with the maximum recommended lifetime dose of high-energy X-radiation over 30 daily sessions. Simultaneously, I also took the chemotherapy drug Temozolomide (aka "TMZ", "Temodar").
While recovering from these treatments, I took a closer look at what had been done to me, using the scientific training I'd received over some time at universities and in industry. I hold a Ph.D. in Chemistry from the University of Texas at Austin. For eight years I worked as a medicinal chemist at a large pharmaceutical company. There I was part of a team of chemists and biologists whose goal was to find treatments for diseases of the brain. That work taught me a lot about gathering and interpreting clinical trial data. It also taught me about interactions between drugs and the brain.
Ironically, it was my own Dr. Neuro-Oncologist who got me to seriously consider abandoning the standard of care, although I'm sure this was not the intent. I had read that TMZ was ineffective in some patients so I asked Dr. Neuro-Oncologist about that. They explained that, actually, all patients benefit from TMZ, but some more than others. If I were to look at the original clinical trial conducted by Dr. Stupp, I'd see that for myself.
So I tracked down the original study and read it — several times. But no matter how many times I did, I came to the same conclusion: Temozolomide has little to no efficacy in about half the patients it's prescribed to. I've written extensively about who these patients are (hint: me), what makes us different, and why I decided refuse further Temozolomide treatment.
Some time before making this decision, I had been doing my own research into drugs I could take in addition to the standard of care. I was inspired by the book Surviving Terminal Cancer, although I've since come to disagree with many of the ideas presented there. I'll write more about that later. For now, it's enough to say that I found what I was looking for: a drug I could get my hands on that had showed some evidence of efficacy against glioblastoma: sodium dichloroacetate (aka "dichloroacetate," "DCA"). I've written in detail about the published research on DCA and my thoughts on it.
Many glioblastoma patients experience a respite from disease progression within the interval between the end of chemoradiotherapy and the start of "adjuvant" Temozolomide. During this period the tumor shows evidence of response. Symptoms stop getting worse or even get better, and MRIs show few notable changes. My wife called this period the "island of stability."
My plan was to start taking DCA within the island of stability. Rather than twiddling my thumbs waiting for the start of adjuvant chemotherapy, I wanted to take the fight to the tumor by smacking it with something it hadn't seen before. It was a nice idea, but things turned out differently.
Before, during, and after chemoradiotherapy, my symptoms got worse and my MRIs showed growing bright patches. Dr. Neuro-Oncologist ascribed this to treatment-induced "swelling." I was doubtful. It's a complicated story that I recount here. The bottom line is that there would be no island of stability for me. By late August 2023 it was clear that the bright spots ("hyperintensities") on my MRIs weren't due to swelling; they were tumor progression. The standard of care chemoradiotherapy had failed. Not only that but my interpretation was that chemoradiotherapy had not hindered my tumor in any way.
On June 20, 2023 I finished formulating a DCA protocol. By "protocol" I mean a reproducible procedure for obtaining DCA, estimating its purity, and self-administering the drug. I let Dr. Neuro-Oncologist know what I planned to do. They said they "couldn't prescribe" DCA but would continue to monitor me. I was on my own more or less for this.
Obtaining a bottle of powder purporting to be DCA is not difficult. I bought one on Amazon and it wasn't expensive. But years of experience synthesizing and formulating drug candidates taught me that white powders can contain all kinds of crap. I worked with a local analytical lab to characterize and estimate the purity of the material I had bought. Satisfied with the result, I moved on to the next step.
Obtaining a bottle of authentic, pure DCA was just the first step. I needed to know how much of it to consume, how often, and perhaps most importantly how to get it into my body in the first place.
But before any of that I needed to answer a crucial question: what would cause me to stop taking DCA? Clinical studies with DCA indicated just one major side-effect: peripheral neuropathy. The Mayo Clinic describes the condition this way:
Peripheral neuropathy happens when the nerves that are located outside of the brain and spinal cord (peripheral nerves) are damaged. This condition often causes weakness, numbness and pain, usually in the hands and feet. It also can affect other areas and body functions including digestion and urination.
The problem with glioblastoma is that it can cause exactly these kinds of symptoms. How would I tell the difference between the symptoms of tumor progression and the side-effects of DCA? Recall that my tumor was centered in the right parietal lobe. As a result, my disease symptoms appear on my left side: left foot; left leg; left arm; and left hand. I reasoned that if anything resembling neuropathy showed up on both sides of my body, I'd stop taking DCA. Multiple clinical studies reported that the neuropathy side effect was reversible, meaning that it went away after patients stopped taking the drug.
Regarding dose and route of administration, the clinical study I was working from (see its supplementary material) notes the following useful information:
… Initially, the half-life of DCA is <1 hour. DCA inhibits its own metabolism and serum concentrations increase, eventually reaching a plateau. The plasma trough concentrations of DCA in our patients remained undetectable for the first 2 to 3 months but thereafter reached therapeutic concentrations. At a dose of 6.25 mg/kg orally twice a day for at least 3 months, trough DCA concentrations were 0.44 ± 0.16 mM. …
In other words, it takes 2-3 months of taking DCA to build to a stable blood concentration after administration. This was even more reason to take a cautious approach. From other studies I learned that there are "fast" and "slow" DCA metabolizers. This is the result of a genetic difference, and I had no idea which I was. It's possible to get tested, but I felt I didn't have the time to try to figure this all out. I also had no way to monitor DCA plasma concentration. In that sense I was flying blind, but I'm not sure knowing how quickly I metabolize DCA would have changed anything I did.
I decided to start at the lowest dose for which no neuropathy was reported. If all went well, I could escalate from there.
As one additional precaution, I made a list of every symptom I was experiencing prior to the first dose of DCA. It was a long list. If something went wrong, I'd be able to refer back to this list as a way to tell the difference between the effects of tumor I already had and DCA.
I took my first dose of DCA on July 24, 2023. I dissolved the colorless, odorless, fine powder I'd received and later analyzed in about 200 mL of water. At this concentration, which is much more dilute than I'd later use, DCA is tasteless. I waited, for what I'm not sure. There was nothing — not immediately after taking DCA, nor the next morning. I felt not a single sensation that I didn't already have.
The units "mg/kg" denote milligrams of drug per kilogram of body mass. For example, if I weighed 100 kilograms, I'd take 625 milligrams of DCA (625 mg/100 kg) to get a 6.25 mg/kg dose. The conversion factor from pounds to kilograms is (2.20 lbs/kg). So If I weighed 200 lbs, my weight in kilograms would be (200 lbs) divided by (2.20 lbs/kg), or 90.9 kg. Expressed differently, the 6.25 mg/kg dose in the clinical trial was equivalent to (6.25 mg/kg)/(2.20 lbs/kg), or 2.85 mg/lb.
No kitchen balance has the milligram accuracy I needed to weigh DCA powder. Fortunately, such balances are widely available on Amazon and inexpensive. Mine (brand "MAXUS Digital Milligram Scale") cost less than twenty dollars. It's portable and included a scoop, re-usable boat, and calibration weights. Battery life has been effectively infinite so far.
The clinical study talks about taking DCA "on an empty stomach." Given twice daily dosing (once every twelve hours) and certain interpretations of "empty stomach," coordinating mealtimes on that schedule can prove challenging. I experimented with the notion of "empty stomach" over the coming months. In the beginning I settled for one hour before a meal. I'd later learn that either one hour before or after a meal works fine.
But when I took DCA less than one hour before or after a meal, bad things happened. I mean explosive diarrhea bad. I mean the loudest fart I've ever heard bad. Luckily I've always been home when I made these mistakes in timing, but it would have been a disaster in any other place. I learned to simply skip a dose if it interfered with a meal, or change the time of the meal.
Here's my current protocol for preparing DCA. At least one hour before or after eating a meal, I dissolve 550 mg of powdered DCA in about 30 mL water. At this concentration, the taste is slightly bitter. Then I drink another 30 mL of water. I do this twice daily, roughly 10-12 hours apart. My current dose is 7.1 mg/kg (550 mg / 77.2 kg). My weight has shifted (mostly dropped) over the last few months, but I've kept the same dose. DCA is extremely water soluble, so I imagine I could easily drop the volume down to one milliliter or lower. But at that point the problem becomes manipulation. I imagine a syringe could be used.
I don't expect to make any changes to this protocol, but it comes at the end of some experimentation. A few months ago, I ramped the dose up to 10 mg/kg over a few weeks. I scaled this back because at this level and with the preparation I was using at the time, DCA upset my stomach. For me, the dose-limiting factor was upset stomach (I called it "the gurglies" for the way my stomach sounded). I think it might be possible to tweak the concentration to get higher doses, but haven't tried.
Until September 26, 2023 I underwent weekly blood labs of the kind I did when taking TMZ. None rang any alarm bells. For fun, I compared my results with those reported in the DCA clinical trial and found good agreement.
In early October I started tapering Keppra, the anti-convulsant I'd been first prescribed way back on March 23. I completed the taper down to zero around early October 2023. About six weeks later I re-started Keppra after what might have been one or two seizures. I've been taking Keppra since at a reduced dose compared to March, and without a repeat.
It's not clear to me whether another symptom, shaky hands under certain conditions, was due to the Keppra taper, tumor progression, or DCA. To be safe, I stopped taking DCA completely in October 2023. Although I wasn't experiencing neuropathy, the symptom was bilateral and it was new. And that worried me enough that I decided to pause DCA and see what happened. I learned two things: first, a subsequent MRI showed that my tumor had spread to the left side of my brain, across the corpus callosum. This could explain the bilateral shakes. Second, one month after stopping DCA, my hands still shook. I concluded that the shakes were due to tumor progression, which was well underway before I started taking DCA.
On November 6, I started taking DCA again at exactly the dose I had left off with, 550 mg. My shakes neither increased nor decreased in intensity, and I could detect no side effects unambiguously attributable to DCA.
At of this writing (January 7, 2024), I'm still taking 550 mg (6.9 mg/kg) of DCA powder freshly dissolved in 30 mL water twice daily, with a 30 mL water chaser — no less than one hour before or after a meal.
I've told people who ask that the best outcome I can hope for from my DCA regimen is exactly nothing. There will be no effect on the tumor and there will be no side effects. The clinical trial I'm working from, although hinting at an effect, was small and messy. This is not to fault the authors, but rather acknowledge the extraordinarily difficult conditions they were working under. My current thinking is that the authors found something that without question deserves to be closely studied in a larger, controlled way. I'm willing to revise this position given clear evidence of efficacy in myself or in a large controlled trial.
And that trial may actually happen. The NIH reports that an upcoming Phase IIA trial of DCA for glioblastoma will be complete by June 2025. But recalling what I wrote in the introduction to this article, I don't have that kind of time to wait. It's not entirely clear to me whether the treatment arm will be given adjuvant TMZ or not. If they are, the patients in the ongoing trial will be doing something I didn't.
I can't help but compare the experience of taking Temozolomide to taking DCA. First, you don't "just" take TMZ, but rather three drugs: the Temozolomide itself; an anti-emetic to control nausea; and an antibiotic because TMZ body slams the immune system, rendering patients more vulnerable to potentially life-threatening infections.
My DCA protocol is just white powder in water. The only side effect of note has been digestive trouble but only if taken within one hour of a meal. No nausea. No vomiting. No fatigue. Nothing. But again, it's hard to distinguish the effects of tumor progression from side effects of DCA.
Having had some time to think about it, I'm starting to wonder whether TMZ could actually be doing harm in MGMT unmethylated patients. It interferes with the immune system, which has been the subject of intense scrutiny as a source of treatments for glioblastoma. I prefer my immune system fully functional so that it can engage with the tumor (if it does), rather than compromised by a drug whose benefit is minimal at best.
Patients whose tumors are MGMT unmethylated face a grim treatment landscape when diagnosed with glioblastoma. The standard of care is based on TMZ, a drug that is at best minimally effective. Much of what lies beyond the standard of care, the Optune device and clinical trials, are administered in conjunction with TMZ. MGMT unmethylated patients tend to fare worse across the board. I can only hope that some day MGMT unmethylated patients like me will have access to a low-side effect, effective alternative to TMZ. Something like DCA perhaps, but with demonstrated efficacy. It seems borderline unethical to continue administering a drug that does next to nothing and which may be causing net harm just because "there's nothing else to prescribe and patients demand a pill."
Knowing what I know now, I would have made some changes in treatment. First, I would have started taking DCA shortly after surgery, and would have informed my medial team of this. I would expect strong opposition to this idea, which I would try to graciously disregard — unless I was being given new information. DCA has an induction period during which it can't be detected in the blood. But given about two months a steady state develops. I'd take the opportunity after surgery and before the start of radiotherapy to raise my blood and brain levels of DCA. I would refuse TMZ — all of it. Again, I'd expect opposition to this idea. I might consider doing the legwork to find out whether I'm a fast or slow DCA metabolizer, but I'm not sure this would change much. Finally, I'd continue taking DCA through radiotherapy and beyond. How long? Good question.