Flavopiridol, One Year Later

I went down to San Diego for my one year check-up after my eight-month trial with flavopiridol (Alvocidib).

I had a very good response to the flavopiridol. I was hospitalized overnight for the first two courses, to make sure my potassium levels did not go overboard as a result of tumor lysis syndrome (although the kidneys can be damaged from the products of CLL cell necrosis, tumor lysis is a nice thing, since it means the evil CLL cells are blown apart by flavopiridol).

My rock-hard abdominal lymph nodes gradually softened and melted away using the drug. This was accomplished by weekly infusions in San Diego, for four weeks in a row, with a two-week holiday in between cycles.

As I've noted here, the drug was not an easy drug to take. The main problem was with the urgent diarrhea that followed a hour or so after the drug, and that lasted through the night. The other side effects I noted were general malaise, about two hours of abdominal cramping and pain, and a fatigue that lasted a few days.

The other, perhaps more serious side effect, was the neutropenia that accompanied the drug. I had to have either a Neupogen series, or a Neulasta shot about once every couple of months. Of course that may have been also linked to my disastrous dalliance with the hated FCR.

If they could develop a version of the drug that didn't have the diarrhea problem, they'd have a winner. Or if it could be administered locally, so I could get home and sleep off the problem, it would be better. (Obviously if the drug was approved, this latter condition could be met.)

My response lasted about the nine month average noted in previous patients. My feeling is that perhaps Flavo could be given for six months or so (since I didn't note any more lymph node softening or reduction in size after that), and then monthly. It's an unpleasant drug, but if it could keep the CLL at bay, I'd gladly do a monthly 'maintenance' dose.

Of course I have no idea if that would work, but that might be a winning idea, even with the drawbacks. Flavopiridol is an excellent drug, it works just as well for a second go-around (rare in any cancer drug), and it has few (but annoying) side effects.

I wonder about its fate as a approved drug. It is effective in over 50% of CLL patients, and in patients who respond, the outcomes are good. But it isn't a cure, nor a lasting treatment, unless it could be given as a maintenance drug, perhaps.

Mixed Results

I'm through with the rituximab infusions that have accompanied the CAL-101 daily pills (150 mg twice a day).

CAL-101 pushed many CLL cells out of the lymph nodes and into the blood. My WBC which has been hovering around 2.1 after a disastrous bout with FCR, went up to about 47,000. It has dropped to 24,000, where it has stubbornly stayed.

I've also had increasing fatigue and a few bouts of day sweats, both of which I associate with CLL progression.

We know that CAL-101 is not a cure. A recent paper that will be presented at ASCO paints a dismal picture of the drug, with only a 33% response rate. It shows that many people drop out of the trial after disease progression. And lymph nodes decreased by only 50%, which means that CLL, which grows primarily in the nodes, is still present in large numbers.

It may be that drug resistance to CAL-101 is more common than we had all hoped.

We are all hoping for a solid treatment that is easy to tolerate and keeps the CLL at bay, if not curing the terrible disease.

As it stands now, it doesn't look as though CAL-101 will be that drug, at least in the population of heavily pre-treated patients such as myself. Perhaps it will do better in untreated patients.

I must admit that it will be great if it works extremely well in untreated patients, but not well in others. It would be bittersweet for us who have been through the mill with CLL.

I've often wondered about the elation of CML patients (chronic myeloid leukemia) who saw the miracle treatment of Gleevic and related drugs, but failed to respond themselves. The elation, and then the crushing disappointment must have been terrible for them.

For now, my lymph nodes seem stable.