Flavopiridol

After much thought and a thorough examination of the options available to me, I decided to go with a flavopiridol trial at UC San Diego. I've been treated at UCSD before, I really like Drs. Kipps and Castro, and I can fly down there and back in a day if I can manage it.

Flavopiridol, also known as Alvocidib, is a cyclin-dependent kinase inhibitor. It has been suggested that it helps promote CLL cell apoptosis, or programmed cell death; it also slows the growth of cancerous tumors.

The drug has an interesting past. It was discovered to have a very profound CLL cell killing effect in the test tube, but when tested in humans, it seems to have no effect at all. The drug was set aside, but 'rediscovered' and looked at again. It seemed hard to believe it could blast CLL cells in the laboratory, yet do nothing in patients. Finally, they figured out that the drug would bind to human serum proteins, leaving precious little available to kill the cancer cells.

After much more experimentation, a different dosing schedule was worked out. The drug is now given in two stages, one dose to bind to the blood proteins, and another to go in an hour or so later, in hopes it will kill CLL cells.

I started on the trial in late July. The clinical trial calls for the drug to be given once a week for four weeks, then a two week 'holiday'. Theoretically, this regime could be given for up to nine months, as long as the disease doesn't progress or the side effects aren't too terrible.

(Dr. Kipps told me he doesn't understand the need for the holiday, since the drug is not myelosuppressive (i.e. it doesn't cause damage to the bone marrow or lead to depressed blood numbers)).

The first two times are down with a hospital stay. This is precautionary since there have been deaths associated with the drug. The cause of death is massive cell death, or tumor lysis syndrome. The massive cell death can dump cellular products into the blood that overwhelm the kidneys, leading to acute renal failure. It is my understanding that the first patient treated with flavopiridol died from renal failure.

The stay in the hospital allows for a quick hook-up to a dialysis machine if tumor lysis syndrome occurs. This did not happen to me. Instead, they managed the blood numbers (they primarily focus on the potassium level) by inducing diarrhea. I can attest that the drug they use to induce diarrhea works very well. I was up and down on the pot about 35 times the first stay in the hospital (my poor roommate was pretty much locked out of the bathroom).

After the first two weeks, the patient is treated in the infusion room.

So far, I've had two stints of four infusions each. The treatment has worked well; my blood numbers haven't changed much, so there is no impact there (although my blood numbers have been very low since my disastrous acquaintance with FCR). The main benefit has been in my spleen and abdominal nodes. I've had shrinkage in the massive nodes in my abdomen and in my spleen.

The main adverse side effect has been my development of a severe aversion to the diarrhea-inducing medicine. I cannot tolerate the taste, the smell, the sight or the thought of this drug, (Kayexalate). I started to get sick after taking this about the fifth time, and I ended up in the hospital vomiting for an hour or so.

What I do now (and I REALLY wish I had know this going in) is to go on a low-potassium diet on Sunday before my Wednesday infusion. If you have a level below 4.0, they won't force this vile stuff on you. So I am VERY, VERY careful to have a low potassium level before I do the flavopiridol.

It is such a negative effect that I probably would drop out of the trial.

The other thing that they didn't do is routinely treat me with anti-nausea drugs before the treatment is started. Instead, they wait until I start vomiting. Dumb! Anyway, I now take my atavin and zofran with me and take it before I start on the treatment. The last time I was down there I only vomited a couple of times.

The other really odd side effect is what happens about four hours after the treatment. I suddenly feel terribly ill, ready to go to the emergency room with a fever and general malaise. However, it passes after a half hour or and hour. However, I am ready to call 911 if I have to.

So, flavopiridol seems effective, but is not the easiest drug to take.