Saturday, October 22, 2016

Programmed cell-death ligands: the trailer

I won't know until mid-November whether or not immunotherapy is recommended in my case. That makes it a little hard to get motivated to research the subject, but I don't want to be doing it at the last minute either. So I've started looking into it. The idea is that I would ``join a research study'' on atezolizumab (trade name Tecentriq, approved for bladder cancer by the FDA last May), assuming certain conditions are met as discussed below. Anyone who is interested can easily find details online, so I'm just going to give the short version.

There is a lovely term ``programmed cell death protein'' or ``''death-ligand'' PD-L1 blocking antibody. The idea seems to be
(this is all based on a cursory survey of the web, and a preliminary conversation with the onc) that PD-L1 is bad because it interferes with good guy immune cells that would like to attack the cancer.  Atezolizumab blocks or inhibits the PD-L1 so that the good guys can do their job.
In bladder cancer patients, this therapy is approved for patients who have had ``platinum-based chemotherapy'' (i.e the cisplatin), yet the disease has still progressed. That is possibly true in my case, but we will wait to see the results of the latest round of chemo.
If the cancer in the liver has been reduced or at least hasn't progressed, my understanding is that the chemo is declared a success and we don't do the immunotherapy. Of course ``success'' in this business seems to mean temporary success, apart from a few rare cases where a complete cure is obtained. One often sees the abbreviation DoR, which at first makes me think of ``dead on arrival'', but actually stands for ``duration of response''. This refers to the length of time before the bad guys start up again. By the way, a key point to be aware of when evaluating statistics is that there is a group of patients who get the immunotherapy because they are too old or in too bad of health to tolerate the platinum-based chemo. Keep this in mind if you come across gloomy death statistics; some of these people were already in bad shape for other reasons.

The second criterion for proceeding with the immunotherapy (according to the onc; the online literature is less clear on this point) is that PL-1 should be (sufficiently ``highly expressed'' on the tumor.  I think the idea is that if it isn't highly expressed, then the success rate is too low to risk the side-effects (see below) or to justify the cost. This is why they first have to send a sample of my original tumor to a lab. (Didn't know they still had it; maybe they keep it in a refrigerator in the lunchroom. Anybody ever see the movie ``The Loved One'' with Jonathan Winters? If so, you'll get the reference.)

In theory, the process of getting the immunotherapy is simpler than the chemo: one 30-60 minute infusion every three weeks (for how long, I don't know). But I assume that many more visits to the clinic are required, for check-ups and so on.

This leaves the big question: side-effects. Some people have died from atezolizumab therapy, but it's a small percentage and I suspect they're generally people who were in bad shape to begin with. On the other hand, there is the usual list of fairly common side-effects: fatigue, nausea, constipation, decreased appetite, and especially urinary tract infection. Plus a host of gruesome but less common side-effects including thyroid problems and eye problems. That last one is a potential game-changer for me. If any kind of permanent eye damage is even remotely possible, I would not do it. Even temporary problems (blurred vision, double vision and redness are all mentioned) might be enough for me to say ``no thanks''.

But it's all up in the air at this point, so I'll just wait and see. Programmed cell-death ligands, watch your step!

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