Steve Kirsch health update

By Steve Kirsch
March 12, 2009

The short story is I'm still alive and well. People are amazed I have cancer. You'd never know. I am currently at a lower level of disease burden than when first diagnosed.

My treatments have included CPR (one dose), solo-Rituxan (several doses), low-dose Rituxan, Enzastaurin, and LBH-589 (which I am currently on).

My strategy was to try drugs that had a low side effect profile yet demonstrated effectiveness. I steered clear of any drug that would weaken me or cause my cancer to mutate to something worse or cause peripheral neuropathy. I switched drugs only when either 1) it stopped working, or 2) something more promising became available. LBH has worked well for me. After just one month, my IgM has dropped by 40% and side effects are minimal. Clinical trial is open at Dana Farber and in Denver, CO.

Kirsch Waldenstrom's Macroglobulinemia Diary documents my treatments and blood counts over time.

The key lessons I learned are this:

• overworked physicians can miss reading your blood work for a week. I had a blood test showing an IgM flare and the Stanford doc didn't read it for almost a week. As a result, I have permanent vision loss in one eye. Moral: You are ultimately responsible for your treatment. Understand the disease and the impact the medication you take and watch for anomalies so they can be promptly treated.
• my platelets plummeted to under 20 with LBH. Moral: don't assume the clinical trial protocol was perfect. If something seems amiss (I had a bloody nose), get your blood counts checked. Also, I had a clue because my platelets were in a steep trajectory. So make sure extrapolating trend lines doesn't put you in danger. Had I not talked to my doc about my bloody nose, I could have suffered bleeding in the brain and had irreversible brain damage. These drugs are powerful. Learn the side effects, learn what to watch for, and don't ignore the warning signs. Ask for help when something doesn't seem right.

The rest of this page was written in May 2008.

In July 2007, I was diagnosed with a rare incurable blood cancer. With current treatments, it's likely I have at least 5 years left. Here are the details of my diagnosis. This page is a quick update on where things stand.

I had my first cancer treatments starting in December of 2007 consisting primarily of 4 doses of Rituxan (a monoclonal antibody which they infuse into you over about 4 to 8 hours) which were infused approximately once a week for 4 weeks.

The Rituxan lowered my disease burden (my IgM level) by approximately 50% after 3 months which is an excellent response to a first treatment.

Due to the great response I got, the doctors decided to do a second round of Rituxan on April 23, 2008. After the first two infusions of this second round, my IgM counts flared (a very common reaction for WM patients to Rituxan) to the levels (3502) that were about 10% lower than where I was before I started treatment (4000).

As I write this, it's been 6 weeks since my last treatment and I'm still flaring. Flares can last from 1 month to 3 months.

The bottom line is that it looks good and my counts are moving in the right direction, but it is very premature to declare victory or success. But we won't know for several months whether this is just a temporary flare, or that the Rituxan result was only temporary and my disease is back at full strength again.

I made a $1 million dollar grant to support the work of Irene Ghobrial at Dana Farber Cancer Institute who I think is doing some excellent research in this area and the treatments she is working on in animals I'm optimistic will work in humans, including me. She is using a two-pronged approach to treating the disease: one drug (AMD3100) to force my cancer cells to go into the bloodstream (instead of hiding out in the bone marrow where it is hard to kill) and another drug (Rituxan or Humax) to kill the cells when they enter the blood. I think it's very exciting and could be in the clinic in 6 months if things go well. While it probably won't permanently cure people of Waldenstrom's, it stands an excellent chance of being a very effective treatment with very low side effects.

I also switched doctors and hospitals. I was at Stanford. Now I'm at El Camino Hospital. Never heard of it? HealthGrades rated them among the top 5% of hospitals in the nation and they were one of only 269 medical institutions in the US to receive the Distinguished Hospital Award for Clinical Excellence in 2008, the fourth year in a row they have done so. So I'm not compromising quality.

My doctor at El Camino is much more flexible with respect to treatment protocols. At Stanford, I was treated "by the book." At El Camino, the doctor has the flexibility to make decisions based on our mutual best understanding of how the disease works and how the drugs work.

There is an excellent case to be made that giving people a lower dose of Rituxan at a reduced dosing frequency may lead to better outcomes. Every researcher I talked with agrees it would be an interesting experiment to make and it is also safe. They also are very excited about learning what the results will be. But my doctor at Stanford will not treat me if the approach isn't proven in a clinical trial. I don't have time for that. So I sought out a doctor who treats the patient based on the patients individual reactions and the latest scientific knowledge about the drugs and the disease, rather than trying to make me fit the profile of the "average" patient.

Did you know that it's one size fits all for Rituxan? No matter what disease you have, no matter what your reactions are to the medication, no matter how poorly you respond, the dosage is EXACTLY THE SAME FOR EVERYONE.

That's bullshit. That cannot be the optimum dose. There is incredible variability even within my extremely rare cancer. It's ludicrous to believe that this is the optimum dose for my disease alone. But to require this dosage on every other blood cancer is even more preposterous. But that's exactly what happens. If you know someone taking Rituxan, I can tell you exactly how much drug they get at each infusion because it's the same for everyone.

Thanks to Stephen Schneider's excellent book, "The Patient from Hell," I have questioned, as some leading physicians are now starting more and more to do, whether Evidence Based Medicine (EBM) is really in the patient's best interest. I believe, and I'm certainly not alone in this, that it doesn't. Erich Loewy, MD, a bioethicist and professor of medicine at the University of California, Davis, argues very persuasively that things are not nearly as black and white as they seem, and that EBM, as it is currently practiced, may actually not serve patients well.  There is a great writeup on this on my page Waldenstrom's macroglobulinemia: Low dose Rituxan.

There is definitely a more effective dose for this drug than we use now. Statistically, it's extremely unlikely that we magically picked the right optimum dosage and that it's the same dosage for all disease and all people.  But until just recently, there wasn't a single clinical trial to try to find out whether changing the dosing improves patient outcomes.

So once my flare stops, I'll start this new low-dose regimen. I'll be making history. I'll be the only person on the planet that I'm aware of to try a lower dose of Rituxan (300mg instead of 375mg/m2) given every 3 weeks to try to cure my cancer.

The CEO of a prominent foundation wrote:

Glad to see your progress on your WM and learn you've found a doctor willing to listen and work with you. Having been in the medical device field for 30 plus years, I couldn't agree more with your approach. Each case is different and needs different care, but unfortunately our FDA drug and device approval system doesn't allow for that. Generally that's were medical judgment comes in and where FDA cleared devices and drugs are used "off label" to achieve more of an empirically derived result. The difficulty is always justifying these off label uses without adequately controlled clinical trials.

Another CEO wrote:

I like your approach. As I might say when you find yourself bailed from an airplane without a parachute you don't want to wait for a proven statistical method of cure. You do your best and never give up hope.

A research scientist at the Massachusetts General Hospital and Harvard Medical school wrote:

Attached is reprint that includes a discussion of my modeling of the impact of chemotherapy of cancer. It shares your viewpoint that the goal of such therapy is the extinction of the cancer clone, that is, the reduction of the number of cancer cells, N, to the point where N=0. This is not an unrealistic goal, as this has proven to be achievable for several specific cancers, such as childhood leukemia and Hodgkin's disease, although it is not a goal that medicine has reached for most malignancies. One might argue that this is because the timing and dosages of chemotherapeutic agents, as they are currently used, have been arrived at entirely empirically, without any sound mathematical methodology to guide one to the most effective ways to use these drugs.

...

But, I should tell you that I have never succeeded in persuading my oncology colleagues to show any interest in taking a mathematical approach to identifying the best ways to use chemotherapeutic drugs.

On the work front, things are cooking at Abaca which is marketing an anti-spam appliance for business. We just had an independent test lab benchmark our results using their real mail flow. We achieved a 99.997% spam catch rate and a .174% average ham error rate. In short, our false positves were 10 times lower than Postini and Postini let through almost 1000 times as many spams as we did. Against other competitors, we did even better!

On the ISP side, we've won every deal we've competed in. These deals will be announced soon. The ISPs like the fact that we can do their entire user base with just a single CPU...even if they have 250 million users! Our processing rate is over 100,000 messages per second which is more than 1,000 times faster than our closest competitor (and that's when the competitor has most of their rules turned off).

If you're not happy with the spam filtering you're getting at work (too many false positives or not enough spam being filtered), or you work at an ISP, we can help eliminate your spam problem!

June 27, 2008: got 100mg infusion of Rituxan

July 1, 2008: Irene's experiments show that in mice, a standard dose kills most of the WM cells within 72 hours of injection. The Rituxan concentration drops very low after 72 hours. A half dose was not nearly as effective. Not clear if 2 half doses are better than a full dose. Therefore, until we know that, it's not clear whether smaller doses are better than the same amount of drug in a larger dose. Not clear how long it takes for the WM to come back.