Tightroping to 90

We saw Deb's oncologist Roger Lange Wednesday (August 20). She's fine, but we got bad news about somebody else.

Even before we knew that Deb had a GIST, Dr. Lange was telling us about the miracle that a new drug had made for one of his other patients. The guy came to Lange just after 9/11 with a huge inoperable GIST. His other doctors estimated he had about three weeks to live. Lange got him on Gleevec, which was still experimental at the time, and the tumor shrank dramatically. The guy went from looking "like a pregnant concentration camp survivor" to looking "like a linebacker" according to Lange.

I've been asking about this patient periodically since then. We've never seen this man and don't know his name, but Deb and I have both developed an irrational attachment to him. As long as he was still doing fine, I felt like Deb had nothing to worry about.

Wednesday we found out that his tumor had started growing again. In response, Lange has put him on a new experimental drug -- so new it doesn't have a trade name yet. The drug is denoted SU11248 and is made by Sugen, a division of Pharmacia. It works according to the same principle as Gleevec, but attacks the cancer at a different point. So it sometimes works when Gleevec has stopped working. (I've just told you everything I know -- more, maybe.) It's still too soon to tell if it will work for him.

His story is not unusual, and we've heard others like it before. Given enough time, a tumor will adapt to Gleevec. A GIST cell can mutate to become immune to Gleevec, and over time Gleevec kills off the GIST cells that aren't immune. At first the Gleevec-vulnerable cells dominate the tumor, but eventually the Gleevec-immune cells do, and then the tumor starts to grow again. Among people with large inoperable tumors, a year and half to two years is about standard for this regrowth to start. (Not that any study has shown this, as far as I know; it's just a rule-of-thumb among people who work with Gleevec.)

It's hard to say what the implications are for Deb. The vast majority of her tumor was removed, and the remainder -- a spot on the surface of the liver and another on the diaphragm -- were cauterized. Some GIST cells undoubtedly survived, but there are no detectable tumors. It's possible that the Gleevec-circumventing mutation hadn't happened yet, though given the size of the tumor it very well may have. Even if it did, the GIST-immune cells were probably a very small minority, so it is possible that none of them survived the surgery, cauterization, and general post-surgical chaos. If none did, then it's very likely that the Gleevec will wipe out the other cells before they can develop the Gleevec-circumventing mutation. If a few did survive, it will probably take a little longer for them to make themselves apparent than in people like the 9/11 patient, who probably had a lot more of them to start with.

But we don't know. So there are two basic scenarios: Either we've heard the last of the GIST, or (probably sometime in 2005) a new tumor will show up somewhere, probably attached to the liver or the diaphragm. Then we'll try SU11248, which will probably have a name by then. Chances are it will also work for a while, and then stop working. If there are two drugs of this type, there will probably eventually be more, so there's reason to hope that we've hit a tipping point, that new drugs will come out faster than the GIST can adapt to them. We call this the tightroping-to-90 plan.

Or maybe we're not at a tipping point and new drugs won't arrive soon enough. There's no way to estimate the odds of something like that.

I'm telling you all this because we're trying to wrap our minds around it. The best way you can help, I think, is for you to try to wrap your mind around it too. That way we'll only have to overcome our own denial, and not everybody else's.

In the meantime, Deb continues to do well.