So it’s official. Another one (therapy) bites the dust.
I spoke to Jessica Lin this morning and I shall not be going back on binimetinib. Hopefully the ocular toxicity I have experienced is reversible. I’m thinking it is. However, were the retinopathy to progress–as it likely would should I continue on any dose of binimetinib–my vision could be compromised. And that’s not acceptable.
Dr. Lin and Dr. Shaw are already in conference per my case. It bites to have an effective therapy waylaid because of side effects. But it happens.
Uncertainty. Once again, embraced. Because right now it is the only thing to hold on to.
When I first started my combo of binimetinib and lorlatinib, I was referred to a retinal specialist, as MEK inhibitors can cause retinal problems. My exam showed some very mild retinal changes.
I had a routine follow up appointment today and I now have blisters on both retinas; yet considered mild retinopathy but concerning enough that I am off binimetinib and advised to go to the emergency room if I experience any visual changes.
I asked the retinal specialist why MEK inhibitors have this potential side effect and she said they felt it was an auto immune response. Well, I’ve got split fingertips, pustular acne, mouth sores, slowed speech, cloudy thinking, and some pretty troublesome neuropathy in addition to my current eye issues. Not to mention high cholesterol, elevated creatinine and low iron. Why can’t killing cancer be easier?
This is a tough spot to be in. I know that binimetinib and lorlatinib have shown efficacy against my cancer. But it is highly possible that the combined toxicity shall ultimately prove intolerable.
This is a good time to remind my audience that this is the explicit purpose of phase one trials: evaluating toxicity and establishing maximum tolerable dose. The actual experience can be as brutal as it sounds.
I have scans tomorrow, review on Monday. And I am certain a discussion as to how to proceed shall ensue.
I am in some sort of semi agitated/unsettled state. It seems I can’t keep my eyes open. But I also cannot sleep. Last week I tried Ritalin and although day one was great (focus! oh rapture!) I also vomited. As binimetinib can make me nauseous I attributed it to that but day two of Ritalin I was intensely sick to my stomach again. And, oddly, sleepy. I took a three hour nap–in the morning. Day three, sleepy, vomiting and there was no day four. Over the weekend I held my binimetinib, in case that was the cause of my droopy eyes.
After emailing Jess about this effect yesterday, I heard back from my scheduler today, asking if I would come in for blood work and possibly a transfusion. The latter because I have also been trending more and more anemic.
In I went, but wouldn’t you know it, my hematocrit had gone up a point and a half. Mystery not solved. The plan for the moment is to continue to hold the binimetinib and I am starting on some prescription iron tabs as well. We shall see.
In the meantime I went to bed tonight around 9:30. My brain was ready but my body was not. First I tried the shaky leg thing, but when that did nothing (sometimes it’s soothing) I found myself making shadow animals on the ceiling. Turns out I’m still pretty adept at rabbit, llama and giraffe.
I was making myself mad though as continuing to lie in bed when you cannot sleep is very quickly fucking annoying. So I got up and made a cup of tea. And now I’m writing a blog. In a couple of minutes I’m going to wheel that bike over to the garage and give sleep another go. Hopefully body and brain will be in accord.
That ugly image of the open wound is my thumb. It is but one of the nine cuts that currently reside on my fingers. No amount of topical steroids, bag balm or liquid skin will make them go away.
I am also dealing with pustular acne. At the moment, maybe nine little spots. I am given to understand that it can get a lot worse.
One is supposed to leave this sort of thing alone. However, I dare you to simply walk around with a pus-filled little (thank god for little) lesion on your face. No, my ego is sound but not that sound. Anything with the word pus in it must go.
Fortunately the topical antibiotic seems to help. Help is nice but I’m shooting for eradication.
I share this with you (TMI, I know) because, once again, I feel it is important to stress, illustrate, underscore the hoops that those of us with cancer will jump through just to stay alive.
Yeah, I am thrilled about that 57% response. Beats no response or progression all to hell. However, side effects that include spontaneously splitting finger tips and acne of the pustular variety are their own special form of devil’s stew.
So ye who are naturally resplendent in health, rejoice. And regard, with both compassion and respect, your fellows who endeavor to become healthy through unnatural means.
What you are looking at are my before and after scans. Evidently I was mistaken about any previous scans after starting the trial–this is my first one. Out the door goes the fever theory (maybe–I kinda like the image of the cancer being incinerated). At any rate, as I am on my back while in the scanner, that is my left upper lobe on the right side of each individual image, and my right on the left. And the scan on the left is the most recent one.
This represents, according to RECIST, a 57% response. If you look closely, there was a whole wad of schmutz on the bottom of my left lobe which has just about disappeared. And the greatest area of consolidation, on the upper right of that lobe, is much less diffuse; some adjacent tumor smaller. There was also some activity beginning on the bottom of my right lobe which is no longer discernible. Without question there’s more unimpeded volume/room for air to circulate–ie: breathe.
Just call me a happy camper. Next on the agenda? I want to boost that response to 70%. And then I plan on sustaining it.
Kumo and I just returned from our second walk today, during which I was taking my customary long strides and deep, deep breaths.
Two weeks ago this was not possible. My fitness had declined to the point that it was, frankly, becoming more difficult to move around.
My lungs have been through a hell of a lot. Not once, not twice—again and again over a period of sixteen plus years. And yet, given the opportunity, they are still capable of a good deal of bounce back. This is something I do not take for granted.
Three weeks ago I would have said that it was unlikely I’d be here for next Christmas. Now I am back to measuring time in years versus months.
Although I don’t have actual RECIST measurements back from the trial radiologist, I do have the assessment of my two oncologists. A “Wow, they do look great!” and a “‘Flipping amazing’ just about sums it up.” And then there was my friend Dr. Jack West’s comments from twitter, which I don’t imagine he would object to my sharing:
Yesterday was all about personal celebration, but today I thought about the greater impact. When I entered this trial, I was advised that the best response had been stability. Although that wasn’t going to be good enough, it was what I was going for. Today I confirmed with Dr. Lin that my scans likely represent between a 50% and 70% response. Which is a heck of a departure from stability. I also confirmed that up until yesterday, stability was still the best overall response.
Today I imagined researchers, other cancer patients, and even pharma execs doing the happy dance. This is so much more than a personal victory–a response of this magnitude represents capital H Hope.
So yeah, this a BFD. And I couldn’t be more pleased.
Alright. So I fantasized that my fever last week was burning out the cancer. I imagined it like toasting marshmallows, with that bad part of my lung just crisping away to ash.
WELL, ladies and gentleman, boys and girls, have I got some news for you. I had a scan this morning and it shows fucking reduction! Never, ever, did I expect to see this kind of positive response at this particular juncture. As I read it (the first time!) I even thought for a moment that perhaps it was a mistake–someone else’s radiology report. But no, that’s my cancer they are describing and it is GETTING SMALLER!
Thus far I would characterize my first several weeks on the binimetinib plus lorlatinib trial as somewhat eventful.
There was that brief episode that led to a few days in the hospital, likely not directly related.
Then the host of new and old side effects. Painful neuropathy (nails and screws is how I refer to it) that is part and parcel of lorlatinib, as well as this perpetual sensation that I am trembling. And the slowed speech–once again, my speaking voiced has the cadence of John Wayne. These are things I am familiar with as I spent more than five years on lorlatinib.
The new side effects are more troubling. Mucositis again—this time the major issue is ulcers on my tongue. Hurt like the devil. Splitting of my finger tips–at one point I had eight different open cuts. They are extremely painful and of course make doing even the simplest of tasks difficult. Retinopathy and dry eyes. The first is mild and simply must be monitored but the dry eyes necessitate the use of drops several times a day and an ointment at night. And then, joy, oh joy, pustular acne. I was advised that the moment it started, I should begin using a particular antibiotic ointment. However, it took two weeks to be approved by my insurance. This really pissed me off. If there is a known side effect to an experimental therapeutic and only one antidote, it should be automatically provided and or covered by the trial sponsor. I finally started on the ointment yesterday, but my face is now covered in small lesions.
And then there are the more serious side effects; I have now had two grade three adverses events. First, the elevated creatine kinase. I had to come off binimetinib and there was a question as to whether or not I would be allowed back on trial and if so, if it would be necessary to reduce dose. Fortunately I am back on and at my previous dose. However, my levels are yet elevated–now grade two.
I am pushing fluids and also have to be very careful about lifting and vigorous exercise; I can’t even use a ten pound free weight. This is frustrating but I am taking it all very seriously as severely elevated creatine can result in both kidney failure and muscle death. No fun.
On Monday I learned that my cholesterol is elevated to the degree that protocol requires me to stop lorlatinib until I am back within grade two range. Elevated cholesterol is a known side effect of lorlatinib and I had been on a statin since I started that trial in 2014. However, once my creatinine became elevated I stopped the statin. Now the cholesterol is a bigger issue than the creatinine so I am back on the statin.
What a circus. Last night I was thinking about the irony that I am dealing with this crazy range of side effects to treat tumors that are just in my lungs.
I find myself wistful for the days of targeted therapy and even traditional chemo. In three weeks I shall have my first scans and a better understanding as to whether or not this is all worth it. In the meantime, my mantra remains eyes on the prize. I will see 2021. And, hopefully, the emergence of other potential therapies.
Ones that don’t have pustular acne as a side effect.
life and breath: outliving lung cancer 