There's no toxin like Cytoxan

Well, there probably is, but new lyrics are running through old songs in my post-chemo haze. “There’s no business like show business” is the tune, and I suppose that having had a round of RCD last week was getting down to business, so that’s why it turned into a rather annoying song looping through my head.

RCD is Rituxan + Cyclophosphamide (aka Cytoxan) + Dexamethasone, which is a protocol used by Dr. Kanti Rai and his group to combat autoimmune disorders, such as AIHA and ITP, in CLL patients. I, of course, am graced with the AIHA (autoimmune hemolytic anemia), a side effect of CLL gumming up the immune system, which periodically leads to bouts of hemolysis, in which macrophages destroy my red blood cells.

I had a variant of RCD for three rounds at the end of 2007 -- click on "AIHA" under "Posts by Topic" on the right for the whole saga -- which held me pretty well. But it did not involve the same steroid program as used in the protocol, which is 12 mg of dex given over seven days. I entered treatment then in a severe hemolytic crisis, made worse by the failure of my hapless Dr. O’Leary to see the depth of the problem, which necessitated a change of doctors in the middle of the red blood stream. Fortunately for me, my beloved Dr. Belle had just resumed her practice. For a couple of weeks there, I was on my own, doctorless, taking 72 mg of methylpredisolone daily in a desperate attempt to slow the loss of hemoglobin, which fell to 6.6 at its worst.

As we began the treatments — first with a little vincristine, which we quickly dropped due to side effects — we stepped down the methylprednisolone. The Cytoxan was doing the work.

Well, chronic disease is chronic disease. And like an annoying, insistent, door-to-door missionary, CLL is always capable of ringing the bell. It did that again shortly before Christmas 2008, which I wrote about here. I was put on 4 mg of dex, upped to 8 mg when that stopped working so well, to control the AIHA over the holidays, then given Rituxan and Cytoxan in January to nail it.

Readers know that Dr. Belle and I have been experimenting with treatments since then, starting with the rather useless R-FFP. I noticed that my red counts were beginning to head south again at some point not too long after R-FFP concluded, so seeking to nip hemolysis in the bud, we did a week of pulsed dexamethasone (four days of 40 mg/day — quite a dose, but similar to what is given to ITP patients) and one round of standard-dose 375mg/m2 Rituxan. It did wonders, for a month, but while the numbers held, the nodes began to creep back. Then we decided to try more pulsed steroids -- this time, a gram of methylprednisolone by IV on one day, plus that standard-dose Rituxan.

The theory, which has been demonstrated in studies, is that there is a synergy between the methylprednisolone and Rituxan that seems to be more powerful than that between Rituxan and dex. But, then again, there's the real world of the particular patient. I have had a lot of methylprednisolone since my AIHA diagnosis in March 2007, with the resulting time to grow refractory to it. We tried the pulsed dose recently to see how I would respond, this being a sort of trial run at the idea of maybe doing R-HDMP.

Well — surprise, surprise — just a couple of weeks afterward the red counts began to show a subtle drop again, I was alerted to this by more-orange-than-average urine (hemolysis warning sign No. 1) that I have described in the past. The conclusion: methylprednisolone is not going to do much for me, and neither is Rituxan along with it.

The RCD protocol no doubt involves the “D” for a reason, and this time we followed it close to religiously, other than my starting the seven days of dex a little ahead of schedule to keep the hemolysis in check over the weekend. I am pleased to report that Friday’s CBC shows a remarkable recovery of the red counts — heck, my hemoglobin went from 12 to 14 in a week, and the overall RBC jumped from 3.91 to 4.43.

Some conclusions

Part of the purpose of this post, which I am dashing off during what is laughingly referred to as a “day off” around here, is to put forward some insights on steroids, AIHA, and treatment based on my experiences. They come with that anecdotal warning, as well as that internet adage, YMMV:

AIHA patients often face a progressive order of attempting to control the condition. First steroids are usually given, but those can cease to work. Rituxan may be next (or may be given with the steroids), and that can cease to work. At that point, you’re looking at heavier-duty chemo. R-CVP is similar to RCD but involves vincristine, which can lead to neurological problems and which by my experience should be avoided unless truly necessary. RCD is gentler and (for me, so far) quite adequate to the task.

It does involve Cytoxan, which is a venerable old toxic drug used in many cancers, and which may be somewhat better than average at getting at 11q-deleted CLL, which I have. Cytoxan (good PDF here, and yes, the more powerful the drug the more fire you play with; this beggar can't be as choosy as he used to be) gives me few side effects, at least that I can see or feel anyway. Lord knows if it's setting up some mutagenic condition that could lead to another cancer, or to further disease resistance on the part of my CLL clones, but remember that line about beggars.

I don't lose my hair, but I don’t have much left to lose anyway. The drug tends to destroy rapidly-reproducing cells, taxing the stomach lining, but it has not given me nausea, only the desire to eat bland food for a few days. I do get GERD, which I find to be easily controlled with Prilosec OTC.

Speaking of food, with all those steroids as well as the Cytoxan, be aware of your glucose. I avoid sugary, carby things as much as possible during the treatment window and I have no hint of diabetes. Still, my glucose, when tested, goes higher than the norm.

I also get more easily fatigued by the changes the drugs wreak in my body, especially when Cytoxan is part of the equation. I have lost at least 15 pounds in a week, much of which appears to be lymph node weight. (People say I look wonderful after chemo.) The neck nodes, which were brought down nicely by the pulsed steroids without the Cytoxan, were brought down much more dramatically with the Cytoxan. I have a lot of abdominal nodes, and for the last couple of nights have been able to sleep comfortably on my stomach — a sign that progress has been made in these unseen areas, too.

Because of tumor lysis — CLL cell kill, with all the dead cells making their way through your kidneys — it is important to stay well hydrated. I drink at least a gallon of water the day before, of, and after my treatment. (And I use allopurinol -– a commonly-given drug that helps control uric acid -– a few days before, and continue it as long as the cell kill remains.) Then I keep on drinking as much water as I can stand. Even with all that, Friday’s blood test showed my BUN was high, not untypical considering all the cell-kill my body had been through.

The water also helps protect your bladder from the Cytoxan, and you should go with the flow, pee whenever you need to just to keep the stuff moving through. Watch the serum sodium results on your metabolic panel, as well — this can dip, so you may want to consider drinking salty water or eating salty foods for a week or so after treatment.

Keep in mind also that steroids are immunosuppressive and that Cytoxan is immunosuppressive, so staying on prophylactic meds -- acyclovir, diflucan, Bactrim -- during this period are part of the tools of the trade of the appropriately cautious doctor and patient.

RCD (dex pills in photo below) works for me where Rituxan alone, and Rituxan with pulsed methylprednisolone (HDMP), do not.

I have been around the steroid block enough now to have some feel for how I react to them. Steroids are excellent though transient reducers of lymph nodes. But they come with enough bad side effects — osteoporsis for one — especially when given in smaller, long-term doses, that they should be used sparingly. (Big, pulsed doses appear to be safer, based on information from UC San Diego and elsewhere, but that's still powerful stuff going into your veins.)

I find that node reduction in steroid-Rituxan combinations still rests largely with the ability of the steroids. (The Rituxan helps more with the cell kill, providing a somewhat deeper, though still shallow, remission.) Once you add Cytoxan, the game changes, at least in me. The nodes reduce as much again as before, and the remission lasts far longer.

Another thing I have noticed along the way is that the mental effects of the 'roids (such as sleeplessness) seem more pronounced when I am on smaller doses than when I have undergone the big pulses. Methylprednisolone at 72 mg and less tended to make me worry things a little, but not at 1 gram. Forty milligrams of dex over four days had the mental effect of drinking water, but give me 12 mg and my brain shoots into overdrive, getting very detailed about things, and I have trouble sleeping. (It should go without saying that dose equivalencies among steroids vary greatly -- this converter can come in handy.)

I expect to be undergoing more rounds of RCD, then perhaps to have a CT scan to see where the nodes stand abdominally, where they are worse than neckly and underarmly, to coin some medical phrases.

Right now I look like a slimmed down picture-of-health, ready to absorb all those laudatory comments from friends and acquaintances who wonder what kind of a marvelous crash diet I've been on.

Living the not-so-good life in Sedona

Our little city of Sedona, nestled amid the red rocks of Northern Arizona, is a resort community and tourist destination. A lot of people retire here to live the good life, or choose to live and work here for the same reason.

It's reasonably affordable, as such places go -- unless you come down with a catastrophic illness and are subject to the whims and foibles of our health care system. I am not talking about myself here. I am talking about a couple in town who lost pretty much everything in a futile attempt to battle the wife's colon cancer. This was reported recently in our local newspaper, the Sedona Red Rock News. Here's a link to the story, entitled "Health system fails Sedona couple." Here are some excerpts:

It wasn’t long before all of the DiMarcos’ days were consumed with medical appointments, arguing with insurance companies and pleading for help from state agencies.

By 2007, their lifelong savings had dwindled to nothing, exhausted by treatments and drugs deemed ineligible for coverage by their insurance company. With no money left, Joseph turned to credit cards to pay for hotel rooms near hospitals, for co-pays and for pain medication.

. . . In spite of hundreds of thousands of dollars of tests and treatment, painful procedures and mind-numbing drugs, by 2008 Andrea’s doctors held little hope for her recovery and she was referred to RTA Hospice and Palliative Care in Sedona. She passed away two months later.

Joseph is left with the memories of a woman he describes as his soulmate, a twin flame with whom he wanted to grow old. He is also left with a mountain of bills, having to choose which one to pay each month.

In the latest print edition is another story (not online), this time about a patient with heart problems who faced the unfairness of the system first-hand. This involves the "churning" of insurance applications, in which private insurers look for an old condition or treatment you may have forgotten to mention and use it as an excuse to cancel your plan rather than pay for the care you desperately need.

My point here is that in any community -- even one of 15,000 people -- there is story after story like this. Health care reform is needed not only for the 50 million uninsured, but also for the many millions more who are insured, only to find that the system fails them when they need it most.

Here's a letter I just wrote to the editor of the News:

I’d like to commend the Red Rock News for its recent series of articles on how failures in our health care system have caused heartache and pain for local residents who are the victims of cancer and other serious diseases.

I am one of those stories. In 2003, I was diagnosed with chronic lymphocytic leukemia. Mine is a fairly aggressive form of the disease and I have required several rounds of chemotherapy. Fortunately, this has been covered by my health insurance, a state-sponsored program for small businesses. But the plan has its limits. It specifically excludes adult stem cell (bone marrow) transplants. I am 52 years old and the expert doctors I have traveled to see out of state (at my own expense, since my plan only covers a limited in-state network), have told me that I am unlikely to see 60 unless I get a transplant. These can run upwards of a million dollars out of pocket, well beyond my capacity to pay.

As you might imagine, private plans that cover transplants want nothing to do with me. Unless there is health care reform in Washington that requires all insurers to take patients with preexisting conditions, I face a bleak future.

I am all for keeping private insurers, but I also strongly favor a public option. Some mechanism has to be put in place to keep private providers honest, as your most recent article about the “churning” of health care applications demonstrates. If people cannot rely on their private insurance in a pinch, then they deserve an option where care is truly guaranteed.

To those who were recently seen protesting here against “Obamacare” and who argue that they don’t want the government managing their health care, I have this to say: What is so offensive about creating a system that preserves your sacred private insurance but also gives people like me a chance to receive life-saving care? Is it really preferable to have penny-pinching private insurance bureaucrats finding excuses not to give you the procedures and drugs you need? I’d take a government bureaucrat any day -- I’ve been dealing with them at the state level for years -- since they don’t have that vested interest in finding ways to deny me, or my doctor. Finally, if you really hate “socialized medicine,” then give up your Medicare coverage on principle. I’d gladly take it.

Sincerely,
David Arenson

THE COMPANY WE KEEP

Counties in blue have some sort of universal health care system. Countries in green are trying to institute one. Countries in orange -- Iraq and Afghanistan -- have universal systems instituted by the United States after they were invaded. Perhaps we have to declare war on ourselves to get universal care?