In March of this year I wrote a piece for this blog entitled "Single-agent Rituxan jumps the shark." In it, I said that Rituxan by itself -- of which I have had three courses over two years -- would no longer do the trick for me when treatment time came around again.
The search for what to do next led to my Doctor Quest, which I have described at length in these pages. I explored options such as Rituxan + high dose methylprednisolone (HDMP), Rituxan + chlorambucil, and even Rituxan + fludarabine, and I picked the brains of a few leading experts. This being chronic lymphocytic leukemia, of course, I got different and even contradictory answers. But in the process I have become more familiar with my case, what the criteria might be for treating it, and the options for that treatment. I also had a chance to mull over the conventional wisdom as well as some opposing viewpoints about depth of remission, long-term survival, and various other things that go bump in the night.
And now, here I am, ready to embark on a course of treatment. I will tell you what I have decided, and why.
I have decided who is in charge
Meeting with some top doctors, as well as some lesser lights, I quickly realized what so many CLL patients learn: four rabbis, five opinions. Or, as one world-renowned expert told me about my treatment timing and prospects, “There isn't a right or wrong answer. I could construct an argument for almost any approach.”
So the one thing I have learned in my Doctor Quest is that nobody knows my disease quite like I do. Or, as I wrote to a friend of mine, “After seeing all the experts and learning all I can, I have learned one thing: my guess is as good as anyone's and it is all a crapshoot.”
This is not hubris. I may be a fairly well-educated patient, but my knowledge of the disease pales in comparison to that of the experts. We patients need our doctors, and I have learned a great deal in my conversations with them. I would not want to be left to my own devices even if I could buy Rituxan at Costco and set up an IV pole next to the living room sofa. Doctors are needed not only for their expertise but also for their skill and experience at monitoring symptoms and managing complications that can blindside us. And not every patient has the time or inclination to make the effort I have made to get to know the lay of the land. Nor does everyone have the same personality type; some people would rather just pick a doctor they are comfortable with and follow that person’s advice. I respect that choice, which seems on the surface to be quite sensible.
For me, personally, it is not enough given the uncertainty that surrounds CLL. I am the recipient of a disease without consensus, a disease termed “heterogeneous” because it is about as individual as a fingerprint, and mine in particular is rather quirky. Understanding of CLL is in flux, old assumptions are being questioned, new treatment ideas go every which way. The experts are left to debate and disagree among themselves. And you and I are cursed with living in interesting times. I wish it were easier to be a patient, but it’s not.
In terms of how to put it all in perspective, someone named Andy once left a comment on this blog that offers sage advice:
“Nothing can substitute for common sense, especially when one's life hangs in the balance. Science is indispensable to the understanding of the pros and cons but when it comes to making a value judgment, science has nothing to say -- that's something many patients (and many doctors as well) fail to grasp.”
So, while I know that I will never have the scientific knowledge of a John Byrd or a Januario Castro, my ability to make the right value judgment is probably equal to anyone’s. And since my life is on the line, I had better become adept at it.
I have decided what makes common sense to me
The more I have learned, the more I am convinced that, as a rule, less is more when it comes to treatment. The least toxic route to disease control is to be preferred to nuking the sumumbitch and risking very real complications that I have written about many times, that CLL Topics has warned about many times, that Dr. Terry Hamblin’s blog has discussed many times, and that basically fall under one category: I done blowed up my CLL and my immune system’s all shot, too.
If there is one thing I fear more than death by CLL, it is becoming sickly and having a lousy quality of life, being in and out of the hospital, being at the mercy of every bacteria or virus that comes waltzing along. CLL means my immune system is in decline -- this is why our immunoglobulins drop -- but why speed up that process?
I said this was my view “as a rule.” There are exceptions. There are people whose marrow becomes impacted, whose platelets and hemoglobin drop to dangerous levels, whose nodes grow to enormous size, and who have no choice but to do something pretty drastic to clear the marrow and deal with the problem. I may be one of those people one day, and if that time comes, I will welcome fludarabine, cyclophosphamide, and god knows what else with open arms and open veins.
But now is not that time.
I have decided I am a tortoise
I know, you’re thinking “What has Dave been smoking? Does he also think he’s the Eggman, coo-coo-ca-choo?”
Let me explain about the tortoise and the hare and how it applies to CLL.
There is a school of thought, the conventional wisdom, that depth of remission leads to longer overall survival. This may make sense in many cancers, but does it hold true in CLL? One problem is that long-term studies are very difficult to do, and CLL is a long-term disease. A must-read is Dr. Hamblin’s “What is the aim of treatment?” series. In it, he posits that the acute leukemia model, in which a cure is the desired goal, may not be realistic in CLL.
“Most doctors who design clinical trials for CLL have trained as acute leukemia doctors, “ Hamblin writes. “Faced with a disease that may span decades they revert to type. Pharmaceutical companies are not much interested in a clinical trial that may last 20 years -- their patents will have run out. Current clinical trials, by common consent, have abandoned overall survival as an end-point; instead they have adopted “complete response rate” and “progression free survival” as surrogates. There are problems with both of these . . .”
Hamblin goes on to discuss this in detail, and I will leave it to you to read his thoughts (see “Resources” below) if you have not already done so. His views may be somewhat heretical on this topic, but that does not make them wrong.
The point is that there is not sufficient evidence, to my mind, that depth of remission will lead to longer overall survival for all CLL patients. The problem is that patients relapse from those deep remissions and are left with fewer treatment choices. Another big-name doctor told me that the weakest spot in CLL therapy is finding things that work on the fludarabine-refractory. And there is plenty of anecdotal evidence, at least, that some patients who get big remissions set themselves up for other big problems in the process, notably immune suppression that can lead to life-threatening complications.
So, will you live longer by running hard out of the gate, or by plodding along only as fast as you need to?
My intuition says to bet on the tortoise.
The tortoise rewarded
Good things come to he who waits, or at least he who moves slowly. HuMax-CD20, the monoclonal antibody, has received fast-track status from the FDA and is now in Phase III trials. Everything I read and hear, officially or through the grapevine, is that this stuff puts Rituxan to shame. It adheres better to the CLL cell, it leads to better cell kill, and being fully-humanized it guards against some of the nasty allergic reactions that can accompany mouse-based Rituxan.
For those of us who have been saying “Do the minimum you need to do, avoid burning bridges if you can, keep your immune system as functional as possible to maximize the effectiveness of new drugs that may come along,” HuMax-CD20 is evidence of our logic, the proof in our pudding. I would be shocked if it were not approved for commercial distribution sometime in 2008, at the latest.
So, how does this tortoise get from here to there?
I’ll conclude my thoughts in Part 2.
Dr. Terry Hamblin's three-part "What is the aim of treatment?" series:
Part I: http://tinyurl.com/qgd2f
Part II: http://tinyurl.com/rxnpt
Part III: http://tinyurl.com/rmjv5
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