Trying (replaces "Damn")

The official scan looked much better than what we were greeted with when the doctor first entered the exam room 30 minutes earlier. At that time, we were told that I would be unable to continue, but we can stay in the trial.

I will keep taking the pills, but I will speak with Dr. BT and the trial radiologist will do a more precise review of how I am doing. I don't think they can or would kick me out of the trial befoer the next scan, but I may choose to stop using brivanib at any time if it gets too hard. Fortunately, I feel strong now; we'll just have to see how long that lasts.

I feel totally wrung out and confused. This is clearly the peril of these "wet reads" (eg, instant review). Sorry to alarm anyone; I will update as I get more information and settle down.
*
Note: This has been rewritten slightly on Aug. 9 to make more sense. A future post will get into my thoughts getting the news we've been dreading -- your cancer has progressed too much for the purposes of this trial, you need to find another approach -- and have them take it back minutes later. I'm still... confused... by the whole thing, but I do think that the decision we came around to was the right one and that brivanib is indeed helping me.

Not good

The CT showed a number of specific changes to my lungs -- they've formed a variety of pits and nodules -- including the collapse of my recently re-operated on right lung. They also found growth in the tumor on my hip muscle and growing lymph nodes up along my spine, which may explain why I've had a such a terrible time in terms of pain and mobility over the last few weeks.

They had already called the drug company when we went in to discuss these results and, indeed, I was taking the placebo. So now I will see if the real drug can do anything for me. Perhaps it can -- I certainly was doing a whole lot better on drug (if only for a little while) than without it.

I was feeling lousy before the news, and now I feel worse: hearing it seems to have (temporarily, damn it!) drained the well of optimism, strength and BS I use to get through this whole thing. Yes, I'll absorb this and move on and learn how to manage the symptoms better, but right now I can barely function.

Gone fishin'

Well, not exactly. We're going to New York again tomorrow for a six-week brivanib doctor's appointment. I will have a CT scan and we will decide where we are at. It's a little hard to know what to hope for in light of the placebo issue. Part of me wants there to be absolute minimum progression, just enough to break the code and re-prescribe the live drug. Part of me thinks that stability (and by this I mean the tumors more or less staying still, not growing 14 percent for technical "stability") on placebo would be great, since I'm dealing with a lot and need all the rest I can get. And, of course, there's the fear that the tumors have broken out of the box and run wild over the last six weeks. I'm trying to deprive that thought of oxygen, though.

And, hell, the tumors could just all be dead. That would be fine. Preferable, in fact.

All this to say that I will probably blog the results if I can, but not much beyond that. L. introduced the dream of seeing the late Picasso show at the Gagosian, which would be amazing if physically possible. (Here's an audio slideshow about the show.) There will also be dinners, of course, hopefully amazing ones. And yes, cocktails on the Soho Grand's luxe couches, where the lighting is so sweet and the ceiling so beautiful that for minutes at a time I can sit there with my lovely wife and feel glamorous, a sensation in short supply in my real life.

Briva-not

Yesterday, my blood pressure came in at 90 over 64 -- nowhere near convincing me that I'm mistaken about having been randomized into the placebo group.

That leaves me with the absurdity of sitting down on my bed each evening before sleep, getting out a formidable white bottle marked brivanib OR placebo, and swallowing four big pills. (Kathy also believes/knows she's in the placebo group; her take on swallowing the probably inert pills was something like "these taste like smarties." I laughed; it beats driving a fist through the wall.)

I've looked at the bottles closely; no clues, no A or B or 0 or 1 at the end of a reference number that might indicate the contents. The pills themselves look and feel the same. I notice -- or think I have -- that the presumed-placebo brivanib pills soften in my mouth quicker than the real deal did; if I don't wash them down quickly, which isn't the easiest thing since they are the size and shape of torpedos, the pills develop a gluey quality. The first time this happened, I thought, "Paste eater!" to myself. (I think that might have been a bizarre insult hurled by a nasty schoolgirl in one of the Lemony Snicket series of unfortunate events books.)

I wonder, but I could just cheat the study. I received a full bottle of real brivanib just as my lung problems started to ramp up. No one confiscated them during or after my hospitalization. I could swap out a pill -- since I imagine the brivanib in my possession will be destroyed when I return it -- and fool around with it and definitively see if there are any differences with what I'm taking now. I could have even, I suppose, taken the real pills instead of the placebo this go 'round, though I wouldn't want any tumor-smashing success mistakenly attributed to the paste pills. I'm also way too much of a goody-goody to break any rules, so the point is moot even though I look at my bagged bottle of the real stuff longingly.

I know this is an inert post (albeit with accidental bonus bad jokes), but it's hard not to get obsessed with this kind of stuff if you are in a placebo-controlled trial. It's hard, even, to leave it behind when you know you are no longer on drug. So chalk this one up for the other folks in the brivanib study who are dealing with this now or may have to deal with it in the future.

Oh, no: placebo

I quickly realized I would probably be able to guess whether I was randomized into the drug or placebo group, but I wasn't in a hurry to figure it out.

When I began the clinical trial, Brivinib spiked my blood pressure to 160/101 and beyond; a normal reading for me, even now, is more like 135/85. After getting out of the hospital, I kept my head in the sand for a few days: I felt fragile and I didn't want to find out I might likely be on placebo. By this weekend, though, I knew I needed to check; you can't walk around unmedicated when you're busting triple digits on both your BP numbers. My reading was something like 110/60. A visiting nurse who came by to pull my stitches the next day got a similar result.

So it looks like I am not on the drug. I haven't taken beta blockers for close to a month now, and Brivinib/placebo is doing nada to my pressure a week or more after I restarted taking the pills. The positive spin, I guess, is that my blood pressure is still low, so perhaps the beta blockers are still active in my system, masking Brivinib's activity. Or it may be the pathways that regulate my blood pressure have adapted to the Brivinib and they no longer go crazy when exposed to it. But in my heart I feel like I'm not getting the drug any more, and I haven't slept a decent night since I found out.

After I got that first, fateful low blood pressure number, L. asked me what I thought it meant, and then she asked me how I felt. The most reasonable questions in the world, but I couldn't answer the second one. How did I feel? I felt terrible. I felt numb. The hardest part of all this isn't the operatic rage -- the shouting, the sobbing, the almost overwhelming pain that yesthisishappeningandnothingcanSTOPIT -- because that makes sense. It might even make you feel better. The worst is the numbness, the feeling that I've lost another little bit of my humanity because I'm too exhausted or sad to know how to respond. I hate the idea of being seen as an invalid by people, because there's so much here; I am boiling over with creativity, love, generosity, life. And other times, like when you finally get some indications (*) that something is working for you and you have to stop because you fell on the wrong side of some BS rules, you feel numb, and drift, and amble through sleepless nights without even knowing why.

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(*) But here's the good cancer voice: "But you're going to get back on the drug eventually if indeed you are on placebo, which you don't actually know you are, you only suspect. Plus, you can actually breathe. And tell them about the other good news besides the shrinkage in your big tumor: The swelling in your perineum, which increased some when your disease was progressing, shrank back during this most recent Brivinib cycle." So there. Thanks for your contribution, Good Cancer Voice.

Oh yeah, the point!

Finished with the doctor.

It's so easy to get wrapped up in this and that tip of the lung or pain the pelvis and forget that there's at least theoretically a point to all these logistics and trips to New York: Getting a drug that will help me. In part because we just had a CT scan two weeks ago, in part because I'm feeling tired, I hadn't focused on the results of today's scan.

They were pretty good!

My disease is stable, and my nastiest tumor actually shrank a fair bit. Another significant one didn't show any change. I'm not sure if big nasty's decline crossed the 20 percent threshold or not -- no formal report yet -- but it's been a long time for me since anything shrunk even modestly.

And, obviously, my lungs look a lot better. How'd that happen?

Ironically, though, today's "stable" (but improving slightly) disease, unlike six weeks ago's "stable" (but progressing slightly) disease, earns me a one-way trip into randomization. We will receive either the drug or placebo today, and I will resume taking some kind of medicine tonight.

The protocol I have praised highly here in the past is now biting me in the ass.

Brivanib optimism

Back again (as of 10:30 p.m. last night), and mostly happy to be here, although it's a little hard to leave the hotel we were staying in behind. It was really nice. 

My health remains in a pretty routine groove, so the interest in the visit was more in what we found out about the study. BT was on vacation so we met the main doctor behind the brivanib trial for the first time. We asked him how he was feeling about the early returns of the trial, and his answer was surprisingly definite. He's feeling really good about it. 

In about six months, they've enrolled about 60 Memorial patients into the trial, and something like 52 of them are still participating. They've seen responses, partial responses, stable disease. They've seen people with stable disease on drug get randomized into the placebo, progress, and get back on the drug and back to stable disease. He said that something like 80-90 percent of people so far were getting some kind of clinical benefit from the drug. "We don't have anything else like that," he said. 

Obviously, "clinical benefit" doesn't necessarily mean what we want it to, e.g. a meaningful increase in life expectancy or quality of life. And this report is anecdotal and premature. But whatever it does for me, it looks like brivanib may turn out to be a good drug, especially for people with liposarcoma.

In another note, we talked briefly about the study's unusual protocol, which sounds like it emerged from many discussions between this doctor and his colleagues and the folks at the drug company. The company needs a placebo group to have faster and more definite proof of the drug's effectiveness. But as an oncologist, the doctor I saw hates placebos. So the study design is an attempt to provide the data the company needs while minimizing (or eliminating) time spent on placebo. Take notes, Ariad.

Chicken bib

So I've been taking brivanib (pronounced with a short vowel: bri-VAN-ib) for almost two weeks now but I haven't said much about it. I'll try to rectify that soon, but first a few quick hits on my experience of the trial so far:

• T. and B. found the name of the drug ridiculous. I guess I never ran "deforolimus" by them. T. started calling it "chicken bib," which I like quite a lot, and B. came up with something along the lines of "brivablaster," which I also like, not least because the drug actually does inhibit fibroblasts. I don't actually know what fibroblasts are, but they sound like things that need inhibiting.
  
• The trial, even more so than the deforolimus trial I participated in, requires a huge investment of time and money, especially if you don't live close to a trial center. I have been to New York three times already for pre-screening and to begin the drug, and we have several more trips coming up weekly until we move to an "easy" once-every-three-weeks timetable. The good news is that hotels are dirt cheap by NY standards, and I am developing an appreciation of the whole boutique hotel concept. (The downside of that is that I'm going to be ruined for when rates jump through the sky in spring.)
• Side effects are little hard to judge so far. My blood pressure redlined immediately (like within an hour) of taking the drug for the first time, and managing it required a fair amount of tinkering with drugs that have serious side effects of their own. Like many folks, I have a short period of dizziness/wooziness shortly after taking the medicine that fades quickly. I feel more short of breath and equilibrium-challenged generally, but the blood pressure medicine plays a role in that also. No gastrointestinal effects to speak of. I have had a couple days where I was almost laid out by fatigue, but I'm not sure what's going on with that. Although my general level of tiredness has definitely increased, the periods of intense tiredness lasting from a few hours up to a whole day have been somewhat sporadic and unpredictable.
• You take brivanib every day, which is kind of nice in terms of routines. Deforolimus was five days on, two days off, and every weekend I would panic at some point that I forgot to take the medicine before remembering that I didn't need to take anything.
• There was some commotion over whether I would need a biopsy (paid for by the drug company) to gather tumor samples. Fortunately, I had enough left over from past procedures to satisfy them. Despite some earlier grousing about the folks at Sloan, they've ended up being pretty solid in terms of taking care of things and getting me started on the study on the earliest possible timetable. Oddly, they are way more relaxed about trial procedure and protocol than the folks at my home hospital; they didn't even mention the BLACK PEPPER PROBLEM until I happened to see it on a sheet I had to ask for.
• Yes, the BLACK PEPPER PROBLEM. I can't eat freakin' black pepper. Nasty white pepper, OK; limited-versatility red pepper, fine. But black pepper -- my cooking touchstone -- is a no-go. Apparently pepper works on some of the same receptors and could compromise the effectiveness of the drug; it's not going to kill you or anything. But I had to become one of "those people," and ask a waitress at a hip restaurant to ask the kitchen not to add any additional pepper to my lobster roll. I tried to explain that it wasn't that I didn't like pepper, it was that I was taking a new medicine that didn't get along with it. Nonetheless, she was bemused and said something along the lines of, "You're allergic to pepper?" No!
• OJ and grapefruit juice are also not happening, though at this point I am mystified by anyone who drinks grapefruit juice, as it seems to be about as dangerous as battery acid for those taking any kind of prescription medicine.
• But hey, even with the new dietary restrictions, at least I'm not one of these people.

Home again

I have about 10,000 thoughts, but they'll have to wait until I can make some sense of them. 

For now: I made it out of Kingston and into Manhattan and started the trial on Thursday. So far, the visible side effects have been minimal -- a swimmy, light-headed feeling about 45 minutes after taking my first dose (and again right now, a little less than an hour after today's dose). The invisible side effect is more serious, but hopefully manageable. As I had been warned, my blood pressure spiked almost immediately after the first dose and stayed high all day. The spin from the research nurse is that getting this side effect is a good thing -- it shows my body is sensitive to the pathways/targets/receptors the drug works on. She also said that they have had great luck in managing brivanib-induced high blood pressure.

'A randomized discontinuation study'

I'll admit it: I felt a little smarter just typing that. I mentioned (threatened?) earlier that I wanted to say a little bit about the brivanib protocol, because it strikes me as interesting and somewhat unusual. I barely have any experience at all with clinical trials, and I've already learned an obvious yet somehow counter-intuitive point: The trials aren't designed to help you. They are designed to bring safe, effective drugs to market as quickly as possible. If they help you, that's great, but it's not the primary goal.

Anyway, the study works like this: You get the drug for sure for 12 weeks. If your tumor grows, you're out of the study. If your tumor shrinks more than 20 percent or so, you stay on the drug for sure. If your tumor remains essentially the same size, you are randomized into a double blind, placebo-controlled group. You may get the drug, you may get the placebo (ugh). If your tumor grows, they unblind the study to find out whether you are receiving brivanib or placebo. If your tumor grew on the placebo but was stable on the drug, they will switch you back to the drug. The protocol requires scans every six weeks, so it looks to me like the time off-drug could be relatively short.