Latest news -- back to the fight

Teresa and I spent yesterday at Memorial Sloan Kettering. Unfortunately we didn't come home with news as good as we had gotten from other recent sessions there.

The short version is this: they found from a CT scan on Tuesday, December 11, 2018 that a few tumors in my liver which had been quiet have now woken up and grown a little (roughly a centimeter in each case). Meanwhile a very small lesion in my iliac bone (a “lesion” is a damaged area, and the iliac is the largest bone of the pelvis), which they’ve been aware of but have never seen any clear indication of malignancy from, has also grown a little, which raises a substantial possibility that this is a metastasis (a spread) outside the liver.

What to do? Well, we intend to fight the disease, which is the strategy that has served us pretty well up to now. But it’s harder, because we’ve already used most or all of the proven strategies. (Though perhaps not all; we may talk with the doctor who administered the radiation this summer, for instance, in case he sees something our oncologist – who was out during our appointment yesterday with a respiratory illness, so we only really dealt with her nurses – did not.) Assuming we’ve tried everything proven that Sloan Kettering offers, we might actually sit tight, not getting treatment. This would not be because we’re giving up, but rather because if the tumors in question are growing relatively slowly, then for my case (somewhat as in many cases of men with prostate cancer) it can actually make sense to be equally patient – while we wait for researchers and clinicians to invent the next treatment that really works.

Or we may try experimental treatment ourselves. Experiments, in the form of clinical trials, are the process by which those treatments that really work are found and developed. Getting a treatment that is currently unproven won't accomplish much if it turns out the treatment really doesn't work. But joining the trial means that you potentially get access to the latest possible approaches earlier than other people do, and if they work you get your treatment before most of the world. 

One especially attractive example of this would be the drug Keytruda, which you might remember successfully pushed back Jimmy Carter’s brain cancer. Keytruda is an immunotherapy drug, and it helps to have the right mutations for Keytruda and other similar immunotherapy drugs to target. So far it doesn’t seem that I have any particularly “targetable” or “actionable” mutations. But some people benefit from these drugs even without having the mutations at which they were originally aimed. The biggest problem with Keytruda, aside from the fact that it certainly doesn’t always work, is that it is expensive, unless they (Merck is the manufacturer) give it to you as a compassionate gesture. That they often do, and we applied for it yesterday.

A second place for experimental treatment is in other treatments being tried inside Sloan Kettering itself. MSK evidently has two sets of first-round (i.e. very tentative) clinical trials going on. One set involves immunotherapy (that is, treatment aimed -- like Keytruda -- at the targetable mutations that I seem to be short of, but that perhaps aren’t essential to the success of treatment). The second set involves, I guess, other  experiments. It looks like we’ll be finding out more about these in the next two or three weeks.

The third place for experimental treatment is, as you’d guess, in other treatments besides Keytruda that are being developed outside Sloan Kettering. Different institutions are running their own trials. There’s a possibly promising one at M.D. Anderson in Houston; another at the National Institutes of Health in DC; and Teresa is applying her formidable web research skills to locating others that show some promise.  

So that’s the situation. I intend to work hard on finishing the 400,000 word version of my book (and if I can also produce a shorter version, more suitable for trade publication, so much the better); look forward to spending time with family and friends; and, as I said, Teresa and I plan to keep on fighting.  

New scan, mixed results

The immediate aftermath of the high excitement I wrote about last time was fairly hum-drum. I’m trying to watch my diet – it’s amazing how many foods may be more prone than others to block one’s intestines – and so far things seem reasonably under control. Foods aside, the main effect of my hospitalization may have been that I lost my regular Friday appointment slot at MSK. Once I got out of the hospital, it took multiple phone calls to get another time – Wednesday, April 11. That meant that my treatment was delayed by the 5 days between when my appointment would normally have been (Friday, April 6) and this new Wednesday time. Meanwhile, it was only on Monday, April 9 that they got me scheduled for a CT scan the following day, April 10, so that the oncologist would be able to evaluate the results of my recent treatment when we met. (They didn’t schedule me for an MRI, which I’ve always had in the past; apparently my oncologist believes in switching between MRI’s and CT scans, though – frustratingly – this change was made without any prior discussion.)

So we came to NYC on April 11. Besides going to MSK, we planned to stop afterwards at New York Law School to see my friends there (and return a couple of overdue books). As it turned out, our timing was very good: we got to see a bunch of my clinical program colleagues (just to be clear: I’m using “clinical” as in teaching lawyering skills, not as in medical treatment) and had a lot of fun talking with them. But I didn’t say much then about the day’s test results; it just didn’t seem the time.

In any case, earlier in the day our oncologist had given us the results of the April 10 CT scan. The results weren’t terrible, but they weren’t perfect either: while my large tumor, off on the left side of my liver, is admirably stable, three smaller tumors over on the right side have grown between 0.5 and 0.9 millimeters. (I asked whether these results could be an artifact of using a CT scan instead of an MRI, but the oncologist assured me that this wasn’t the case.)

Growth is not what I wanted, though it’s still very good that the growth isn’t in newly emerging tumors and that it’s all still confined to my liver. It’s also good that my liver function tests are all in the normal range, so once again my loyal liver cells seem to be able to do their thing despite the presence of the tumors. And despite this tumor growth, when my oncologist checked my abdomen she couldn’t actually feel my liver – which suggests that the tumors aren’t affecting the liver’s overall dimensions.

Over a year ago, when I had just started on the clinical trial using the pump to deliver chemo right to the liver, I had something similar happen: everything was stable or smaller, except that one tumor had appeared and grown. Apparently that one rogue tumor is one of the three that are growing now. A year ago, the fact that there was any tumor behaving this way was enough to knock me out of the clinical trial. Now that I’m not in a formal trial, but just receiving treatment – through the pump again – the Sloan Kettering reaction hasn’t been as dramatic.

Our oncologist thinks that the stability elsewhere in my liver indicates that the chemo I’ve been receiving through the pump over the past several months is still having a positive effect – just not everywhere. So the question is what to do. What she did on April 11 was to give me another dose of my current chemotherapy, which will continue to flow to the liver via my pump for the next two weeks. Then, at my appointment next week – also still not quite scheduled – we’ll consider multiple other options. These include:

(1)  Trying to destroy these three growing tumors. There are a bunch of ways to attack individual tumors, but the ones the oncologist mentioned use radiation, either by putting radioactive beads of a substance called Yttrium on or near the tumors or by hitting them with radiation beams. One particularly interesting option is proton radiation, which evidently can be aimed with more precision than other forms of radiation; we’re not sure, however, whether MSK offers this. I like the radiation idea, since it really seems like there’s something different about these three tumors as compared to the rest. I believe that the biopsy done on one of them after it first appeared showed a different genetic mutation than my other biopsies have found, and certainly their behavior has been different from that of my other tumors. Also they’re in a spot, the oncologist says, where they can be attacked without risk to other parts of the liver.

(2)  Continuing the current pump treatment and perhaps adding a systemic chemo drug that wouldn’t go in via the pump but instead intravenously, to affect my whole body directly; that might in the process also jolt these three growing tumors in my liver.
 

(3)  Immunotherapy: evidently our oncologist can get the drug Jimmy Carter took for his melanoma (keytruda) quite easily as a “compassionate use.” This drug was great for Jimmy, but of course my cancer isn’t the same as his. (The fact that it’s so easy to get this drug as a “compassionate use” – that is, a use for which the drug hasn’t yet been approved by the FDA – is one indication that the “right to try” legislation that Congress is currently considering may really be unnecessary, but that’s another discussion.)
 

(4)  Immunotherapy plus: Sloan Kettering is doing early-stage clinical trials using combinations of immunotherapy and chemotherapy. There’s some ground for believing that two complementary attacks are better than one. (Just by way of explanation: immunotherapy aims to get your own immune system working more effectively against the cancer; chemotherapy simply tries to kill cancer cells directly.)
 

(5)  Targeted medicine, aiming at vulnerabilities created by particular genetic aspects of my tumors; these also would be early-stage clinical trials at Sloan Kettering. Unfortunately, so far my tumors haven’t shown any terribly attractive targets for attack this way – but a few weeks ago Sloan Kettering did a new blood biopsy which may turn out to suggest some promising ways to proceed.
 

(6)  Clinical trials not at Sloan Kettering; Sloan Kettering is really good but there are several other places that are really good too, and each place tends to have its own projects under way.

The good news is that there are all these options. That really is good news, though I’d certainly have preferred a longer period of stability on the current chemo regime. Now we have a lot of studying and thinking to do. Teresa’s putting her formidable internet research skills to work to update the list of possible clinical trials she compiled months ago, and I’m going to be studying up too – while continuing to write my book!

Back on the sauce

I mentioned in my last post, on January 8, 2018, that back on December 29, 2017 Sloan Kettering had finished tapering off my steroid treatment, and that I hadn’t been feeling so well since they did so. (I’d been receiving the steroids to deal with the inflammation of my liver that I’d experienced in late 2017, apparently a side-effect of the chemotherapy; meanwhile I was on chemotherapy “holiday.”) After that post I continued to not feel well: my energy was low, my digestion upset. Meanwhile I wasn’t receiving any treatment at all: the steroids had been tapered off to zero, and the oncologist felt that my December scan showed I was doing well enough that I should continue without chemotherapy unless my tumors resumed growing. It was, frankly, a bit weird to have no treatment going on, while something – I didn’t know what – was happening to my body. But I described all this to the Sloan Kettering folks (special hat tip to my oncologist’s nurse, with whom I spoke in detail), and they decided to schedule my next scan a little earlier than they otherwise might have.

So I got scanned on January 23. Each time I do an MRI I’m puzzled again about exactly what I’m supposed to do as the patient. Not long ago I was told that I was breathing too faintly, which seemed to be the result of my falling asleep during the scan; this time the MRI staff said it was fine if I went to sleep, but then they redid one part of the scan because I was breathing too heavily! I’m not sure what a good scan actually looks like – to my eyes they all seem pretty hard to decipher – but it does appear that whatever a good scan is, there are multiple ways of going about getting it. Some MRI staff favor one approach, some another. For sure, the human interaction between the patient and the MRI staff is important to the successful use of this high-tech tool.

But in any case I did well enough to produce clear images. We learned the next day, January 24, that what the images showed was renewed growth of my tumors, mostly but not always growth measurable in millimeters. And that in turn meant that our oncologist decided chemotherapy should resume – that very day. I’m back on the combination of FUDR and mitomycin, administered through separate channels of my intrahepatic pump. The FUDR dose has been reduced, to limit the chance that my liver will again get inflamed, but the oncologist is confident that a reduced dose can still be clinically effective. I’ll be on the current infusion till this coming Wednesday, February 7, then off for about two weeks, and then, assuming my liver has tolerated the resumption of chemo all right, the next round will start on Friday, February 23.

It would have been better news, of course, if my tumors were still stable or even contracting. But this news is at least clarifying: I wasn’t feeling well, and it’s plausible to think that the reason is that the tumors were growing. Tumor growth, it seems, takes its own toll on my body. The best news is that since I’ve gone back onto chemotherapy, I’ve definitely felt better. At first it seemed possible that this was because of the steroids which accompany the chemotherapy, since after the steroids were tapered off to zero at the end of 2017, I was actually on a steroid holiday as well as a chemotherapy holiday. But at this point the amount of steroid I’m getting via the pump is very small (something like a milliliter a day, and flowing into my liver rather than directly into the rest of my body), and so I suspect that the reason I’m feeling better is that the chemo itself is working and I really am better. Hopefully the next scan, probably a month or two from now, will confirm what I think my body is saying.

Whether it does or doesn’t, though, it’s clear that it’s time for us to think seriously about clinical trials or other treatments, since at some point the FUDR/mitomycin combination may lose its impact. Teresa and I have just been to the Cholangiocarcinoma Foundation’s excellent annual conference in Salt Lake City, where we learned a great deal about the current state of the science and the clinical trials that are getting underway. I wouldn’t say we got a lot of answers, but we certainly came home with many new questions – some of which I’m sure I’ll be writing about in future blog posts.

An unexpected chemotherapy holiday

Last Friday, December 29, we went in to Sloan Kettering for the biweekly appointment that’s become routine. It had been some time since I’d actually received any treatment except the steroids that were going through my pump directly to the liver to treat the liver inflammation I experienced earlier in the fall. But for the past month or so our oncologist had been tapering off the dose of steroids, and so we had come to think that this time the steroids might actually end and the chemotherapy resume.

The oncologist herself was away, but we met with the nurse practitioner who is part of the practice group. She began by telling us, with some excitement, that this time they were going to put glycerol in my pump. She seemed to feel this was good news, but to us it was not. That was partly because glycerol is not chemotherapy; it is, instead, what they put in the pump when they’re basically taking the pump out of service for an extended period, up to six weeks or so. It was also not good news to us because we were both so taken by surprise to hear it. When we thought about it all afterwards, it did seem that the oncologist had mentioned, back at our December 14 session, that the next time they might put in steroids (again) or glycerol, but this hadn’t registered with either of us. And the reason it hadn’t registered with us is that we had no idea that Sloan Kettering’s plan was to continue my break from chemotherapy.

This led to what diplomats call a “full and frank exchange of views” between us and the nurse practitioner, and to an appointment to see the oncologist a week early, or in other words on January 5. As it turned out, we never had that appointment, because on January 4 New York was one of the targets of a major storm, which in turn was followed by a really impressive cold snap, and the oncologist kindly called me at the end of the day on January 4 to propose that we simply talk then and there on the phone.

So we did just that (with Teresa and me listening to the oncologist on speaker). This conversation was much more reassuring than the one we had had on December 29, and a big part of the reason was that the oncologist now explained to us what her reasoning was.

As readers of this blog will recall, the scan I’d had shortly before the December 14 session had produced an encouraging and surprising result. Even though I hadn’t received any chemotherapy at that point for about two months, the scan showed that my largest tumor was now smaller; and that of the smaller tumors, some were a little smaller, some unchanged, and some – not many – were a little bigger.

We knew that already, though, and we’d assumed that the next move would be more chemotherapy to follow up on this encouraging scan. But our oncologist felt otherwise, and that seemed to be for two reasons. First, she appears to feel that this is about as good a result as I’m predictably likely to get with current possible treatments. It’s not impossible that some other treatment would get better results, but that’s unavoidably uncertain, so the “bird in the hand” is my current, pretty good state. Second, she is worried that renewed chemotherapy might renew my liver inflammation too. Liver inflammation, she reminded us, is really not good: I could wind up with a liver stent, which among other things then increases the chance of infections. It’s much better if my liver continues to go about its business as it should – and as the latest bloodwork shows it is.

So what to do? Actually there’s a simple answer. The oncologist plans to have me get another scan by early February. If the results are as encouraging as the previous one’s, we might very well wait again. But if the results show that the cancer is on the move, then it will be time for new treatment.

Which new treatment? One possibility is the same chemo I was on before, the chemo that caused the liver inflammation, but at a lower dose. But another possibility is a clinical trial. The oncologist told us – and this was news too – that she’s always keeping the possibility of a clinical trial in the back of her mind. Apparently there are some underway at Sloan Kettering that she’s thought about, but I don’t think she wants to go in that direction as long as I’m doing as well as I am, on the “bird in the hand” theory. Should we apply to one of these in advance? That doesn’t work, she explained; the slots in the trials open and then are filled very quickly, so I have to be ready to move in that direction when I start applying. (She also mentioned that liver inflammation can make me ineligible for clinical trials, another important piece of information.)

Meanwhile, the impact of stopping the steroids hasn’t been entirely trivial. It may be that I’ve in effect been running on steroids for the past months – and now that I’m definitely not doing so, since the dosing with steroids has ended, I’ve been very tired. At the same time, every use of the pump seems to upset my digestive system, even the injection of a substance like glycerol that’s been chosen for its innocuousness. But I’m hoping that these various problems will go away in due course, and if so I’ll be able to wait for the next scan, and perhaps then for the scan after that, and so on.

For now, we’re going to be researching clinical trials. Sloan Kettering’s may be the best, but on the other hand they may not be, and we’ll be trying to find out as much as we can in the coming weeks.