Triple Option Offense

Just seems like an appropriate analogy given Tech's new head football coach and his vaunted triple option.

We are proceeding as expected and as I discussed in my last post.

I have a successful transplant, but the insidious Richter's Transformation form of diffuse large B cell lymphoma (DBCL) has long since escaped the reaches of the new marrow and blood. Eventually, the theory is that the graft would could catch up with it. After all, the lymph system is part of the immune system and goes hand-in-hand with the marrow and blood. But the DBCL is very aggressive and fast growing, so it will stay well ahead of the graft's ability to catch it. There is no known long term or even medium term cure for DBCL using chemotherapy. But it is possible to kill the disease in the nodes for four to six weeks.

So, first of all, we need a short term solution to get the tumor load of the nodes down. Then we need a medium term solution - which could actually become a longer term solution if this next step works out. This medium term solution is the Sunesis drug that I have talked about. It actually doesn't have a name yet, but goes by SNS 032 in the clinical trials. It is not a conventional chemotherapy, but rather is a kinases inhibitor. It attaches to DBCL cells, prevents them from progressing, and causes them to die off as they should (apoptosis). See the following website for a little better description http://www.sunesis.com/science/oncology/MOA032.php

So the plan, which has already started with chemo as of yesterday evening, is to temporarily kill the disease already very active in the lymph nodes. We are doing this with a strong chemo regimen that goes by the cryptic name of Hyper CVAD, part A. I have had this before in the summer of 2006 and it's not too bad. Now part B is a different story; it pretty much kicked my buns and my bone marrow, too, last summer. But we're hoping part A will do the trick and we won't have to go to part B. If this goes to plan the disease will be in temporary remission for four weeks or so.

Then we will start the SNS 032 study. The protocol for this study requires that you be off all chemo and monoclocal antibodies (MAB's) for at least three weeks. So if Hyper CVAD does the trick for four weeks then we can start the SNS 032 study before the DBCL starts to roar back. That timing might be a little tricky because each time you kill back the DBCL you are actually just killing the weaker members of the colony, so each time it comes back it will be with the stronger members of the colony coming back which will just be that much more aggressive.

The SNS 032 protocol is for a six hour once a week infusion for four weeks. Then you wait and see. Seems like we do a lot of that here. The Hyper CVAD/A is a five day continuous regimen so I will be done with that Sunday evening.

I'm not sure what the expected remission time might be with SNS 032. They don't know either. Hence the clinical trials to see just that.

I will be in a late Phase I group or early Phase II group. Either way the maximum tolerated dosage will already be determined. I would hate to be in an early Phase I group because the chances of it doing you any good at the minimum dose would have to be slim.

In the meantime, if we don't damage the graft too badly with the chemo it might acually have a chance to join in the fray. Ultimately we have to depend on the graft to be the permanent solution, but the Sunesis drug might also turn out to be a long term treatment.

Now for a little primer on clinical studies plus a little political commentary. The way clinical trials work is that after the mice, rats, and other varmints are experimented upon, they move to the two legged varmints. Phase I trials are mainly seeking the maximum tolerated dose by humans, the two legged varmints. They are performed on small groups of humans starting with the minimum dose. Then they progress to another group using a larger dose. They repeat several times while increasing the dose each time. At some point they reach the maximum dose and further prove some efficacy of the drug as well. The next step is a Phase II trial where the drug, at the maximum tolerated dose, is given to a much larger group of people to test the percentage and degree of response on a more statistically valid number of people. After that they move to Phase III using an even larger group of people while testing the drug using placebos in some of the participants. After successful Phase III testing it goes to the FDA for approval.

As you might can imagine, development of new drugs is a multiple year process requiring the expenditure of vast resources by the drug companies. So don't complain about the cost of medicine too much. We have the best medical care in the world because it is free market based. Socialized medicine does not support this kind of development. A vote for socialized medicine will be a vote for poorer medical care in the future. There are ways to increase the number of people insured in this country without adopting socialized medicine, so don't be duped by politicians who want to be all things to all people - it can and will blow up on all of us.

About half, I guess, of the doctors at MD are not from the U.S. As Dr. Keating said, he would rather live in his native Australia but he can't pursue his work there. Google Michael Keating and you will find that he is arguably the best CLL doctor in the world and could practice anywhere he wanted. Dr. Tam, his very sharp Aussie assistant, has just moved back to Australia because his visa expired and our tightened immigration laws don't allow for exceptions anymore. My bone marrow doctor is Indian. This is very real. We are benefiting from our system that attracts the best talent in the world. Adopt socialized medicine and much of this talent won't stay here. A word to the wise from someone who is in the thick of it.