Tag Archives: Alk mutations

And this is on a good day

I’ve been out of control the past few months—driving, flying and riding trains. Taking care of shit and visiting folks. Having adventures. Tying up loose ends. And damned if it isn’t fabulous that I have the energy to do all this.

PF-06463922 has been my drug of choice (makes it sound a little bit sexier, no?) for more than seventeen months now and my cancer remains stable. That’s the longest I’ve ever gone on a therapy without progression and continued stability is my new mantra. The troubling side effects that I experienced initially have mostly disappeared although time management and memory remain a challenge and the neuropathy in my hands and feet is not going away. Some days I feel like I’m living with a very young child and someone who is elderly—they’re both me.

I am sharing my latest radiology report to lend some perspective. As I look so very healthy, (healthier than most healthy folks) it’s easy to forget that since the beginning of this journey (April of 2005), I have never been cancer free. That’s right—removal of my lower left lobe and four rounds of cisplatin and taxotere was not enough to push this crud out of my lungs. Since then I have always had a varying degree of cancer hanging around. At the moment, the situation is pretty good but this is what a good day looks like:

Lungs and Airways: Central airways are patent. A 1.9 x 2.8 cmlingular subpleural opacity and 5 mm subpleural right upper lobenodule (image 40) are unchanged from 10/7/2014. Several 3-4 mmpulmonary nodules are unchanged from 10/7/2014 and are found in theright upper lobe (image 29, 37, 46, 52) and left upper lobe (image45, 54). A 5 mm subpleural anterior right upper lobe ground glass nodule (image 48) is unchanged from 11/19/2014. Subpleural ground
glass nodule in the anterior right upper lobe measuring 6 mm (image
45) is unchanged from 10/7/2014. A 4 mm superior segment right lower
lobe groundglass nodule is unchanged from 1/19/2014 (image 43).
Additional left upper lobe groundglass nodules measuring up to 6 mm
(image 50) are unchanged from 10/7/2014.

If I was just being diagnosed we’d all freak out. As it stands, this is a great report.

My cancer and I have been sharing the same body for almost eleven (known) years now—that’s 1/5 of my lifetime. Wrap your head around that. During that time I have been to the edge of possibility and back again, a looping cycle of dying, hope, disappointment, loss, more hope and a whole lot of living mixed in.

It can be a real mind fuck.

The Boston Globe has a new online medical magazine called STAT. I was interviewed (print and video) for an article about the emotional roller coaster faced by terminal patients who are given the opportunity to try high risk experimental therapies. Clinical trials offer hope (our favorite word) but responses are not guaranteed and when they do occur, are of unknown duration. All that uncertainty can really mess with your head.

http://www.statnews.com/2015/11/04/for-cancer-patients-breakthrough-drugs-are-saving-lives-but-wrenching-souls/

But I know more details would be helpful…

My beautiful daughter on a particularly fateful day.

My beautiful daughter on a particularly fateful day.

Is there some fresh way of saying ‘It’s been a challenging time?”

No, probably not. And besides, challenging is a euphemism; a gentled version of what I wish to convey.

It’s been a difficult year, and the year before that as well. Adjusting to life alone, the continued progression of my lung cancer, a short stint on Xalkori, and then at long last admittance to the PF-06463922 trial. But it has not been without wonder.

About that trial…

I went in with low expectations, as my second secondary acquired mutation (G1202R) is highly resistant to all ALK inhibitors, although results in the lab indicated that my cancer could still respond at higher doses. I entered in the third cohort, at a dose of 75 mg. I was delighted when my cough began to abate almost immediately. But then four days after regular dosing started, I began to experience marked shortness of breath and the sensation that something was caught in my windpipe. I was coughing a lot and some of it was streaked with blood. The following morning there was a small clot of blood in my sputum, but my shortness of breath had abated. However, upon awakening the next day I coughed up yet another small clot. Hemoptysis is one of those things you just can’t ignore, so I sent a text message to Dr. Shaw, who was away at ASCO.

While waiting for a response, I received the phone call from my stepfather Jim telling me that my mother had passed away.

And that phone call was followed by one from a member of the clinical trial team, telling me that I’d been scheduled for an urgent CT scan, in order to rule out a blood clot or pulmonary embolism.

Fortunately my daughter Jemesii had the day off and pretty much insisted on meeting me at the hospital. I was going on adrenalin at this point and don’t know what I would have done without her. In prep I blew two IV’s for contrast (these veins are getting tired) and ended up having a vasovagal response (never happens to me) so I earned some time out in the recliner with some intravenous saline. And then after the scan wrapped up Jemesii and I headed over to the Termeer Center for the results.

And this is when things got really weird. The attending physician said I had neither an embolism or a clot. “How about cancer?” I asked. “Is that all gone?”

“Well, no…but…” she said, and then read from the report:

Lungs and Airways: Status post left lower lobectomy. A mixed
attenuation lesion in the lower portion of the remaining left upper
lung is significantly smaller than on the prior exam now measuring 2
cm x 1 cm x 3.2 cm significantly smaller than on the prior exam where
it measured approximately 8 x 7 cm in diameter. A small right upper
lobe mixed attenuation lesion (series 4, image 330) measures 6 x 7 mm
minimally decreased from prior measurement of 7 x 9 mm. 4 mm region
in the left upper lobe seen on series 4, image 339 is not
significantly changed. A nodule in the right upper lobe seen on
current examination (series 4, image 314) and on prior examination
on 66, image 155 now measures 4 mm in diameter down from 6 mm. And
unchanged region of atelectasis is present in the left upper lung
near the left hemidiaphragm. Additional nodules. Similar in size to
prior exam. No new nodules are seen. There is no evidence of new
pneumonia or pulmonary edema.

I had begun regular dosing six days prior and an 8 x 7 cm chunk of tumor had melted away to a mere shadow of itself. It was just unbelievable.

Stunned, Jemesii and I decided that a good meal and an even better glass of wine was in order. We raised a toast in honor of my mom. And then we raised another to the future.

Word of the day: Optimism

I just made an appearance in the Massachusetts General Hospital Newsletter: Targeted Cancer Therapies Make MGH Patient Optimistic — MGH Giving.

Serendipity I guess, as it looks as if I’m about to enter my third clinical trial for a targeted therapy. On the 28th of April I will have a CT scan and then meet with Dr. Shaw. The expectation is that the scans will show progression; (but it sure would be nice if that expectation was inaccurate) and the plan is that I will sign the paper work to enter the PF-06463922 trial. If it’s a go, washout begins the following day; I will likely start the trial two weeks later.

In the meantime, I’m getting excited. Teeny bit nervous, but overwhelmingly (yes, it’s true) optimistic. Here’s hoping the third times a charm…

A Bear behind

I’ve been gone for awhile now and I feel a stranger in my own blog. I apologize for such an extended silence—I know that in this community the lack of an update is worrying. So let me start by saying I’m okay: not exactly jump up and down great, but hanging in there.

By way of explanation; I am happy, happy, happy. Mentally, I have never been better. However, physically the situation is a little more complicated as it would appear I’m not responding to treatment. Although I’ve not had a CT scan since starting back on Xalkori, my cough, nocturnal bronchorrhea production and a troubling shortness of breath suggest that my cancer is spreading. In a few weeks, I shall likely start my third clinical trial for an inhibitor that targets both ALK and ROS-1 mutations:  PF-06463922.

I am mindful that it is a blessing to continue to have options. I am also entirely cognizant of the fact that if I don’t respond to the trial drug, those options will be rather limited. It is a sobering realization and yet I continue to focus primarily on the positive aspects of my ongoing survival.

For instance, yesterday was not only Easter, it was Peter’s seventeenth birthday. I was diagnosed with lung cancer in 2005 just before Peter turned eight; two weeks ago I quietly marked nine years of surviving post-diagnosis. Happy Birthday Peter and I am thrilled to be able to celebrate with you!

Life really is remarkable—in all its ups and downs. My own has been topsy turvy for some months now and at some point I felt the need to pull back from blogging and simply concentrate on the day to day business of restructuring existence; more on that later.

First, a little personal history: it was just over fifteen months ago when I resumed chemotherapy. Simultaneously, my marriage was hitting the skids. I felt sick, scared, lonely, trapped and was well on my way to becoming someone I find intolerable—an unhappy person.

Without a doubt, I had hit my personal low point and for the first time, I considered stopping all treatment and simply saying enough. Briefly, that. Instead I took a step back and assessed the situation. It wasn’t going to be easy, but I began to formulate a plan to not only survive, but to prevail.

pre·vail
priˈvāl
verb
1.
prove more powerful than opposing forces; be victorious.
“it is hard for logic to prevail over emotion”

My first priority was Peter’s immediate future, and to that end much hard work went into the private school process. As you know, he was accepted to Phillips Exeter Academy where I am happy to report he is thriving. I am particularly proud of the fact that he qualified for the novice crew team this spring—it turns out rowing is something that Peter really enjoys and has the potential to be quite good at.

My second goal was rather short term, and that was to get through chemo. I did, and after six months of infusions, enjoyed almost nine treatment-free months. Even though my cancer progressed, my body got stronger, and I really needed that physical strength when it came time to move.

And what a move it was. Deciding to separate and ultimately get divorced after more than twenty one years of marriage was huge; particularly under the circumstances. Obviously, it is not a decision that was made lightly.

My dear friend Melinda has remained my guardian angel throughout this process, offering counsel as well as emotional and financial support at various junctures. We’ve been pals (and partners in crime) for almost five decades now and I simply can’t imagine life without her.

I’ve also had some help from a surprising source. At that low, low point many months ago, lying in bed one night after chemo, I felt the need to be both protected and held. I searched my imagination for the appropriate companion and found that it was a bear that I was looking for. I could not only see this bear, I could feel its presence beside me. And I asked this large animal to hold me close; to keep me safe. In exchange for this protection, I told the bear that when I died, it could eat me.

Now this may sound really bizarre—a little crazy even. But, to me it was a perfectly fair exchange. I truly believe that we are all part of one living system, and that when we take our final breath, our energy is dispersed. To be eaten by another creature is a logical repurposing of energy—we do it ourselves every time we dine on something that was once living (plant or animal). I realize some of you may be horrified—and once again I offer my apology. However, know that for me the current tradition of embalming a body is anathema–and cremation is not much better. If I cannot be eaten, I would rather decay and become part of the soil.

Some weeks ago, there was a social quiz on Facebook–‘What is your spirit animal?‘ I took the silly thing out of curiosity. It was already obvious to me what my spirit animal was and I was certain the quiz would get it wrong.

Well, surprise, surprise, my spirit animal is The Bear. Ha! The questions really were seemingly random, but somehow, someway, it turned out right.

Bear really does have my back.

As it turns out, not quite enough (of me)

The word from the lab looking for the PD-1 protein in my biopsy is that there weren’t enough cells (cancerous or otherwise) for a thorough analysis. If it is determined that enough tissue was ‘banked’ after the biopsy, a sample will be resubmitted. Dr. Shaw is not particularly optimistic.

So, the plan for the moment is to watch and wait. We will rescan in November and as long as I don’t become significantly more symptomatic, my situation will be reassessed at that time. In lieu of a PD-1 antibody, I could potentially return to one of the ALK inhibitors which I previously benefitted from:  LDK378 or Crizotinib—although as the LDK is still in trial, I’m not sure how that would work. Chemo remains an option but given the slew of side effects, I would say it is the least attractive choice. What I’m really hoping is that I can hold out until the next ALK inhibitor comes to trial (rumored to be end of this year or beginning of next)—the timing could be just right for me.

In the meantime, my plate is plenty full. I’m looking for a place to live as well as a means of support. I realize that statement implies much and answers little; I’ve got a lot to process and when the time seems right, I will discuss this new chapter in my life.

The world loses a very bright light: Sarah Broom

Sarah Broom:  photo by Shane Wenzlick (phototek)

Sarah Broom: photo by Shane Wenzlick (phototek)

Last Thursday I was up before the robins, in order to get Peter ready for a 5:30 a.m. departure for Washington DC with his classmates. After rousing our sleepy boy, I quickly scanned through my inbox. There was a message from my friend Sarah Broom, with the subject In memorium. I hoped to hell it was the title of a new poem but my heart was heavy as I opened the email. It had been sent by Sarah’s husband, Michael. Sarah had died.

As I hurried Peter out the door, I kept the news to myself. Already reeling from the Boston Marathon Patriot Day bombings, I felt an intense need to protect Peter from additional sadness and worry as he went off on what was intended to be a holiday.

After returning home, I crawled back into bed and fell right to sleep. When I awakened several hours later, I immediately recalled a dream:  I’d been sitting on the floor of a closet that was not mine. Most of the clothing was gone, but there were some beautiful objects on the shelves, shrine-like in presentation and fashioned from polished brass and ivory colored lace or coral. The door to the closet opened, and a stranger asked me what I was doing there. I gestured to the space around me and said, “I am so lonely, and this reminds me of the forts we built as children.”

For the past few months, I had spent many a night imagining Sarah, Thao and myself running, climbing, jumping, flying. Young and strong again, with scabbed knees and cheeks flushed with pleasure. Invincible.

My special relationship with Sarah began almost five years ago. When I took my initial dose of crizotinib in 2008, I was the fourth person in the world with NSCLC and an ALK mutation to do so. Sarah, who lived in New Zealand, had directly preceded me on trial as number three. Through social media and a common acquaintance (number two in the trial, our friend Kevin), we began a dialogue.

Initially, our communication was infrequent. With time, emails segued into long telephone conversations. A little over a year and a half ago, Sarah came to Boston for treatment, and we were able to spend some actual time together. Although she soon returned home to New Zealand, our sessions over the phone continued with renewed intensity.

Sarah was brilliant; a poet with a doctorate in English from Oxford in addition to a master of arts in English from Leeds University. Hers had been a tough road: Only thirty five years old and pregnant with her third child when diagnosed with lung cancer, Sarah advocated fiercely for the sort of care not readily available in New Zealand. For more than five years she endured the side effects of multiple treatments and a hopelessly aggressive cancer, always with unfailing optimism, courage and devotion to her family.

In our lengthy chats we talked of the things most friends do:  love, life, relationships. Books, creativity, our hopes and dreams. But we also discussed our illness and, of course, dying. In a way that was extraordinarily open and free from pretense.

I loved Sarah and felt intensely connected to her. I knew she was dying. In fact, the afternoon before I opened the email from Michael, I felt a certain shift in the universe and was certain that it had to do with Sarah.

I am devastated. However, my loss pales next to that of her family. Also, I know that Sarah had made peace with what was coming and that she is now free from suffering. She will live on in our hearts and in her own words, and although the earth may now be a bit dimmer, the sky is brighter still.

And when I walked out last night

it was cool, the coldest night this winter,
and when the stars asked me to join them
in the ache of their bareness, I let them
take me, and they carried me between them,
clusters of stars all along my body, and I arched right back and pointed my toes and fingertips,
and was as long as ever you could imagine
and they did not let me go.

by Sarah Broom

 

Hits and misses

From the inside looking out this morning

From the inside looking out Saturday morning

The blizzard rolled in right on schedule Friday, but fortunately, we were graced with a big dump of snow but never lost power; nature in all its glory is sometimes best appreciated from a snug environ.

I had my third infusion of pemetrexed/carboplatin on Thursday. As the last round turned out to be so manageable, we decided to ramp up the platinum a bit, and for the first 48 hours, I felt pretty good. However, yesterday I skipped my afternoon zofran and began ramping down on the dexamethasone as well. By early evening I was seriously nauseous, and experiencing some pretty intense heartburn and a headache. I took a compazine, and when that had no effect, added zofran and dexamethasone. Soon I was feeling better again–I can’t begin to imagine how difficult chemotherapy must have been before the advent of steroids and antiemitics. Thanks to an ambien, I was able to sleep, and hopefully today I can again back off on medication.

So—lots to share. I think I’ll start with the visit to the Avon Breast Center at MGH. After the concerning mammogram on Tuesday, a sterotactic biopsy was scheduled locally. However, I immediately contacted Dr. Shaw and asked about having a consult at MGH instead; if the situation required treatment, it only made sense to coordinate my care right from the start.

Well, the magical Dr. Shaw got me an appointment on Friday afternoon. Because of the impending storm, it needed to be cancelled, but they were able to squeeze me in Friday morning instead. Once there, I met with the surgeon, who performed an exam and immediately found a lump (that had been missed previously) in my left breast as well. And then I had some more mammograms done, this time using a 3D imaging machine. After a short wait, more close-ups on my right breast, and then an ultrasound of my left breast.

The conclusion: likely benign fibrocystic changes in the left breast and a 99.5% chance that the microcalcifications in the right breast represent non cancerous changes. So I won’t need to undergo a biopsy and instead will have a repeat mammogram at the Avon Breast Center in six months. The moral of this story would seem to be, whenever possible, (and particularly when your medical history is complicated), get yourself to a center with the best diagnostic apparatus available as well as the expertise to interpret those results.

So that was great, great news. A good thing too, as my scan prior to chemo on Wednesday was not quite as encouraging:  “Mixed treatment response with interval decreased groundglass opacity in the left lower lobe, though slightly increased let lower lobe consolidation and slightly increased mixed solid ground/glass opacities in the right upper lobe.

In addition, the results of the initial genetic sequencing of the ALK mutation are in (it remains to be seen if full genetic sequencing can be performed, as my biopsy  sample was quite small and will require a cell line to be grown in the lab—something that may or may not be possible). The secondary mutation that showed up post crizotinib (S1206Y) is nowhere to be seen. In its place is G1202A, also a missense mutation on the solvent front, but unfortunately one which confers a good deal of resistance to all ALK inhibitors. This will potentially limit treatment options, and the mixed treatment response may necessitate a change of course sooner rather than later.

I am focusing on the fact that except for the few days post chemo, I am stronger than I have been in months. In fact, although I still have a small amount of wheezing and an occasional cough, the copious amount of  nighttime sputum has disappeared. Hopefully the resolution of this troubling side effect correlates with the positive response. However, given the mixed response, I do wonder if there is a chance that the resolving groundglass opacity might have been an inflammatory response to the LDK378 (pneumonitis has been observed as a rare side effect in patients treated with crizotinib).

At any rate, there is no way to know and the important thing now is that I am feeling better. One more round of pemetrexed and carboplatin and then, unless a subsequent scans reveals significant progression, I will go on pemetrexed (Alimta) maintenance. One round, one week, one day at a time.