Chemotherapy Day 1: Lift off!

23rd April, 2021

Today begins my chemotherapy. I will endeavor to keep a diary of the procedure, how I feel, and my overall thoughts/learnings. Today was full of infusions and the regular daily routine.

Prednisone

I’ve been taking this steroid as tablets for the last week, which produces an interesting psychological effect. I feel in “fight or flight” mode as if there is some threat, and the body must be in an active state. There is a brain fog that dissipates in the evening. I take Prednisone (120 mg) in the morning typically.

Prednisone makes my beard grow faster. I have needed to shave every day the last week, which is unusual for me. The final effect of Prednisone is that it elevates blood sugar during the day. It takes a few hours for this effect to kick in, which is harder to handle for people with diabetes. My body has dealt with this well, only spiking blood sugar to 7.5 units at peak in the afternoon. My roommate, Eric, is not so lucky — his sugar is hiking to 15, and he must take insulin to handle Prednisone. The keto diet I have put myself on helps with glucose control.

Gameplan

Today, they will give me the first big hit of chemo. This first hit comprises many chemicals, and I will provide an overview to make sense of the mix.

We can break down the chemotherapy chemicals into five groups:

1. Systemic cocktail: This is chemo put into the body through infusion, and it will go everywhere. My cocktail has three agents — C1, C2, and C3. Their respective names are Vincristine (C1), Daunorubicin (C2), and Cyclophosphamide (C3). They have their beautiful stories we will get into later. Infusions are sent into a vein in the arm, and it lands right next to the heart. There is a catheter inserted to enable this.
2. Neuro cocktail: Cancer can be in the central nervous system. All scans indicate otherwise, but, for safety, I am given a neuro cocktail against cancer in the central nervous system. This cocktail also has two agents — C4 and C5. Their respective names are Methotrexate (C4) and Cytarabine (C5). This cocktail also has dexamethasone, is a steroid, to help alleviate some of the Adverse Events caused by C4 and C5. Nurses administer the Neuro cocktail via some lumbar injection.
3. Antagonists: This is an exciting class of drugs. They act against some of the chemo elements, dulling some of the effects and preserving their other products. Antagonists are usually supplied two days after the chemo cocktails. One example of an antagonist used in my chemo is called Folinic acid (A1). The second is Dexamethasone (A2), an antagonist against C4 (Methotrexate). These are the only two antagonists in my chemo regime for the next four weeks.
4. Defense elements: Chemotherapy has a long history. Perhaps one of the hardest things for the medical system has been to get patients to stick to the regimen. Some side effects develop and cause the patient to drop out. Therefore, they give some defensive drugs against the most common uncomfortable side effects of this therapy. I’m receiving three drugs in this class — D1 (Emend), D2 (Palonosetron), and D3 (Uromitexan). D1 and D2 act against the sensation of nausea or vomiting. D3 helps the kidney metabolize by-products of the chemo elements and prevents urinary tract disorders.
5. Regeneration signal: To understand this class, let’s realize that many of these drugs will plummet the production of normal cells from my bone marrow, also called Bone Marrow Suppression. Bone marrow suppression is needed so that cancer cell production is suppressed. Once the chemo is far enough along, and enough battles are done, the protocol gives one substance called GCSF (Granulocyte Colony Stimulating Factor) to tell the bone marrow to start regenerating and produce blood. As you can imagine, this signal will come later in the cycle. As an aside, I was in the production facility for GCSF for Intas in Ahmedabad as an intern way back. I am seeing this molecule from the user side now.

Now, what did they do today? They gave me the systemic cocktail (C1, C2, C3) as an infusion. They also gave me defense elements D1 and D2 as tablets and infusion, respectively. We will start D3 shortly, and it will take the form of injections for 6 hours all the next three days. Pretty simple, I feel like a cyborg!

The neuro cocktail will follow in a day or two.

How I feel

Pretty much the same. My urine has turned pink, but that is an expected side effect.

Thought of the day

As I go through the journey, many new thoughts will take shape in my mind, and I will cast them here. Thought for today is that humanity has the tools to gather information about the cancer enemy, but not the means to leverage that information effectively against that enemy.

For my disease, they have collected bone marrow samples. We can visualize the blasts (cancer cells) under a microscope and stain them (K1 = Knowledge 1). We can do flow cytometry to understand what different kinds of proteins are present on the surface of these blasts (K2). We can do a panel of limited genetic tests that indicate the most critical mutations in the blasts (K3). If we go further, we can do a whole-genome sequence of these cells to determine how their genome behaves (K4). And if I pursue it doggedly, I might be able to do some epigenetic map of my blasts as well (K5). All this knowledge is there to be plucked at a relatively low cost. K1, K2, K3 are already being run in parallel. K4 will cost a few thousand dollars out of pocket. K5, perhaps 10X more. We can understand every blast element — how it differs from the rest of the cells, how to recognize it from the outside and what it is producing inside.

The chemo plan, however, is entirely independent of this knowledge. The particular cocktail I indicated earlier would be given to any T-ALL patient, no matter what the intelligence gathered from the enemy. There could be two of us with cancers very different but in the same cell type, and we’ll go through the same cocktail and protocol.

Why? It’s down to the limitations of manipulating biological matter. We don’t have accurate toolsets to take in this information and intelligently evolve a remedy that hits the enemy based on this intelligence. Lacking this capability, doctors mostly ignore much of the surveillance of cancer itself. The only use of intelligence is to get some estimate of how “risky” leukemia is. They know from history that cancers with a particular type of mutation usually return at higher rates than others. They use this epidemiological data to tell the patient what to expect of their disease (how frequently it might return) after chemotherapy.

The opening battles of World War II provide an analogy. In the early war, Germany defeated France handily. We take this fact as a given today, but it was a massive surprise when it came. France had the larger army, with experience from World War 1. They had also invested in building massive defenses against Germany for the last 20 years, given the previous war experiences. Why did it happen?

It happened because France was fighting the previous war mentally. In World War 1, both armies dug trenches where soldiers would hide, and they would shoot at each other in a battle of attrition. Months and years would pass with no gain or loss of territory on either of the two sides. The nature of the word was a static battlefront. The French expected the German attack in World War 2 to be similar — a static battlefront and war of attrition.

But something significant had shifted — tanks and airplanes had been perfected from 1917–1938. Inside a battalion of tanks, armies can move fast. With airpower, they can hit strategic targets behind the enemy’s line. These two inventions re-introduced mobility into war. The Germans had realized this potential and developed a strategy of Blitzkrieg, which focused majorly on mobility. There are many examples where they sacrificed materials and land to gain mobility because they saw the value of this new method of warfare.

So were the French defeated. They were committed to a defense plan assuming Hitler’s armies would behave like World War 1 German armies. No intelligence about the enemy changed their mind and made them revisit their strategy. The French saw the Blitzkrieg in action across Eastern Europe before they were invaded, but they missed this intelligence to devise a counter. They were fighting the last war, not the current conflict.

My doctors at UniSpital Basel, and humanity more broadly, are like the French in early World War 2. Just like one could see the Blitzkrieg in action in Eastern Europe, we can gather a lot of intelligence on my cancer. But, our minds are committed to this cocktail. Intelligence about the enemy does not matter in the cocktail design — yet!