Sunday, August 16, 2009

The chemo monster mash: FCR vs. FCA

An interesting therapy comparison has come out in recent days, worth a mention to those who want to update their scorecards.

In this corner, weighing in at a zillion tons, breathing enough fire to melt Mt. Fuji, is our current champion, the Godzilla of CLL clemotherapy -- FCR (Fludarabine, Cyclophosphomide, and Rituximab, Genentech's long-standing anti-CD20 monoclonal antibody).

And in this corner, causing the earth to shake with the whip of its newly-minted tail, is the Mechagodzilla of CLL chemotherapy -- FCA (Fludarabine, Cyclophosphamide, and Arzerra — aka ofatumumbab, Genmab’s competing anti-CD20 monoclonal that is now very close to approval by the FDA).

We all know that the loser is going to be Tokyo. And the winner is . . .

Both, or neither, depending on how you look at it!

Genmab just announced the Phase II results of a tr
ial of 61 chemo-naive patients who were treated with FCA. Those who received the largest dose of ofatumumab (which also used to be known as HuMax-CD20) got a 50% complete response rate as measured by the 1996 National Cancer Institute CLL guidelines. (According to Genmab, the CR rate was 32% in patients who received 500 mg of ofatumumab and 50% in those who received 1000 mg. The overall response rate was 77% in the 500 mg group and a slightly lower -- go figure! -- 73% in the 1000 mg treatment group.) Obviously, the study is ongoing, so we don’t have any idea how long those “complete responses” will last.

Compare Genmab's results to those reported by the respected German CLL8 study group in 2008 in a trial of 817 patients randomized to receive either FCR or FC. The FCR group received a 52% CR rate using the 1996 NCI criteria. Assuming some basic equivalency between the studies, that’s a two percent difference, statistically insignificant.

on-free survival in the German study was 76.6% at 2 years in the FCR arm and 62.3% in the FC arm. But the difference for overall survival was not significant (91% v 88% at 2 years).

(MD Anderson has been providing its own ongoing retrospective, non-randomized information that paints a rosier picture of FCR; it is worth noting Dr. Terry Hamblin's comments here.)

Which brings us again to the perennial question: What's the "best" choice for your first therapy, and how does that impact what you
do after relapse, when it's time for that second act that we often tend not to think about?

In my case, having pretty much used up Rituxan, it’s going to involve some Arzerra in the hope that it works better as a second-act agent, which it does appear to do. It is now being considered for FDA approval for those who are considered double-refractory to fludarabine and alemtuzumab (Campath), neither of which I have had yet -- but neither of which, the more I use chemotherapy of any kind, is going to work as well as it would have had it bee
n my first choice out of the box.

So welcome to the boxed-in world we CLL patients live in. What do you chose for your first act? How does that impact what you choose for your second? (And, transplant planners, how do those choices impact that third and probably final -- and I mean "final" in the hopeful "cure" sense -- act?)

Which brings us to another bit of recently-reported information, floating around the air like Mothra:

“First-line fludarabine not superior to chlor
ambucil in older CLL patients”

In a study of patients over age 65, the German CLL Study Group randomized 95 patients between fludarabine and chlorambucil.

Progression-free survival was similar in the fludarabine group (19 months) and the chlorambucil group (18 months); however, clinical significance was not reached. Overall survival was also similar between the two groups (46 months vs. 64 months), but again, clinical significance was not reached.

The bottom line is that fludarabine provided a m
ore robust response (as well as more bone marrow toxicity) but in the end that deeper remission didn’t mean the patients were living any longer, at least as of this writing. Keep in mind the OS non-difference between FCR and FC as reported by the German CLL8 group.

Of course, the trick is to track these things over a much longer time period, to see how overall survival of Regimen A vs. Regimen B goes on year after year after year.

Unless, of course, your CLL isn't giving you a decade or two to watch all the data dribble in.

Then you have to pick your monster and place your bet.

Hello Kitty, anyone?

The Hello Kitty Darth Vader, a sure sign that the end of civilization is near.

Sunday, August 09, 2009

The dog days of August

Anyone who has Googled "chronic lymphocytic leukemia" has run across references to the disease in dogs and, more rarely, cats. If you give Fido some chlorambucil, he goes on merrily chasing his tail, usually for a normal life span.

Recently I received a phone call from someone who read my letter to the local paper in which I explained that I have CLL and that I support
health care reform. The caller left a message on my answering machine. She said she supports reform also, and then began to talk about her dog, which was recently diagnosed with CLL. If it would not be a bother, she asked, would I mind calling her back and telling her a little bit about the disease and what might be done to treat her dog?

When Marilyn and I heard the message, our reaction was the same: laughter, of the disbelieving kind. I don't mind talking about CLL to fellow patients, or to my neighbors, or to a complete stranger who has some interest in the disease. But I'm not a veterinarian.

My gut level response, to my surprise, was anger. I love animals, and I like dogs, but I have seen too many friends and acquaintances die of this disease. I have seen too many struggle with impossibly difficult choices. For every great remission I have seen great disappointment. I have spent almost six years struggling with CLL, not always successfully. If I thought the last six years were bad, the next six promise to be worse. So pardon me if I don't have a lot of energy left over to counsel people whose dogs have leukemia.

Sometimes I think I'm being a little hard-hearted about this, but I cannot bring myself to call her back. I know she means nothing by it, that she's probably not aware that a CLL patient might develop some emotional baggage after awhile. Is she being a little insensitive? Or am I being oversensitive?

I empathize with her and her dog, but all I want t
o say to her is "Use your freakin' Google."

Am I right or am I wrong?

Saturday, August 01, 2009

The runaway shopping cart CLL fitness test

On Tuesday night we were at Bashas', our favorite local supermarket, which is built on a sloped lot. After we loaded the car with groceries, our shopping cart, to make a long story short, escaped. It was heading downhill, and at first looked like it would come to rest against a metal railing. But the gimpy wheel that had annoyed us during our trek through the store came into play, setting the cart on a subtle curve right toward someone's car, and it was picking up speed as it went.

It would not be right, I thought, to allow it to bang up someone's vehicle, so I took off after it, running as fast as I could. I caught up with it about three feet from the car it was heading for, which I saved from a scratch or a dent. I was not so lucky. As I grabbed hold of it, both it and I fell, me on my left side.

I bruised my shoulder, got some long scratches on my leg, and the bumpy asphalt was particularly unkind to the area just below and to the left of my knee. This was not helped by the fact that I was wearing shorts, leaving bare skin to come in contact with the ground.
I came away with a bloody sore about 2" by 2", part of it black.

Nurse Marilyn drove us home, I took a shower, and she administered Neosporin and a bandage to the wound. The next day we saw our primary care doctor, just to make sure everything was OK. This is where the CLL comes in, because if I did not have lowered immunity -- made worse by my neutrophils being at their nadir due to recent chemotherapy -- it's unlikely that we would have felt the need to be so cautious.

The doctor complimented Marilyn on her bandaging ability, and the black spot was determined to be asphalt, which had embedded itself in the skin, and which we were told would gradually work its way out as the wound healed. He was pleased to hear that I was on prophylactic Bactrim, which is one of the precautions I am taking while doing RCD (Rituxan, Cyclophosphamide, and Dexamethasone) therapy for CLL and AIHA (autoimmune hemolytic anemia). Apparently, Bactrim is used to fight staph infections, among other things. I was sent away with a clean bill of health, or as clean as a CLL patient with a bloody sore can get.

One of my first reactions to the incident, besides "ouch," was to put it in the context of CLL. It was as if I had been subjected to an impromptu physical fitness test: Did I have enough hemoglobin to run at full speed and tackle a shopping cart? Were my platelets numerous enough to insure proper clotting of the wound? Was my immunity good enough to avoid infection? Have my bones survived steroid therapy well enough to avoid breaking or fracturing when my 200-pound body hits the ground?

I was pleased to have passed on all counts, and to know that I can still endanger myself by stopping speeding metal objects.
After awhile, one learns to take nothing for granted about life with CLL, especially after having lived with periods when the disease, in the form of its AIHA complication, has impacted my ability to do things like I used to.

There is a fitness scale for cancer patients, called the ECOG performance status, named after the Eastern Cooperative Oncology Group. The scale runs from 0 to 5, with 0 being the best,
"Fully active, able to carry on all pre-disease performance without restriction." For most of my CLL life, I have been at that level. But the AIHA, with its red-blood-cell-destroying hemolysis, has put me at ECOG 1 or 2 at times. Two, for example, is ""Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours."

I suppose I am lucky that I am generally a 0, as the shopping cart chase demonstrated. I hope to avoid ECOG performance status level 5, which is described succinctly in the chart as "Dead." Those at level 5 don't put in much of a performance, evidently.