Category Archives: LDK 378

The downstream effect of two miracles of science

My friend Dr. Tom Marsilje wears a number of hats–devoted parent, dedicated scientist, cancer patient and absolutely amazing advocate/activist.

Tom holds a special place in my heart and personal history but sometimes I have to stop and remind him; we both suffer from chemo brain, a subject he recently covered in his column for the The Philadelphia Inquirer.

He was in town briefly last week so we met for lunch and a photo op in front of Miracle of Science in Cambridge. I mean, how could we not.

Linnea and Tom: two miracles of science

Linnea and Tom: two miracles of science

After snapping our selfie we headed down Mass Ave to Flour, one of my favorite little cafes. Lunch banter was about any number of things including Tom’s relatively new role as a writer, and he noted that it makes him feel good to be really making a difference. I just looked at him incredulously before exclaiming “Dude!”

At this point I should remind you that Tom codeveloped LDK-378, the second ALK inhibitor I was on trial for. Also known as ceritinib and now marketed as Zykadia.

I then used my finger to draw an imaginary line on the table. “This” I said, “is my lifeline. And this is where I started taking ceritinib. No ceritinib and my lifeline stops right there.” And then, for further emphasis: “I am alive because of you and don’t think I ever forget that, even for a moment.”

By this point I was getting a little weepy. I went on to say that if Tom were a war hero rather than a scientist who developed a lifesaving drug for a pharmaceutical company, than his role would not be so seemingly anonymous and that he would be celebrated. But that the lack of accolades in no way diminished what he had already accomplished, which was to extend the lives of so very many ALK positive cancer patients. Including yours truly. And that I was grateful to the moon and back.

Such a tight connection between the individuals who come up with these drugs and those of us who take them. A lot of cause and effect going on there and to think that Tom and I would have the opportunity to also develop a human connection is just way, way cool. This guy had my back long before he ever met me (but must of known of my existence as an ALK+ individual). Gotta say I’ve got his back now but sometimes that just feels like hanging onto contrails as he’s jetting around with astounding energy and putting his fine intellect and experience to work as an advocate/activist for patients with advanced cancers. I feel both honored and blessed (and damn fortunate) to have him in my life.

Which leads me to this closing thought: maybe we should nave a national hug a medical researcher day. Followed by a bunch of bang up fundraising.

xo

And this is where the road forks: 12/12/12

L1020594Tonight I will take my final dose of LDK378. At 7 am sharp tomorrow morning, I will report to radiology/surgery to get prepped for a needle core biopsy. I am hoping that it is uneventful (no pneumothorax), and successful: that sufficient cancerous tissue can be harvested and that the mechanism of my resistance will ultimately be determined. Also on the table–possible gene sequencing.

It’s been a good run; about fifteen months on LDK. I am exceedingly grateful for this deposit in my time bank, but I look forward to the possibility of ramping up my quality of life again. As it stands now, I will be starting chemo (carboplatin/alimta) next week, so it’s a given that I am going to feel worse before I possibly feel better. I’m taking the long view though…

My instructions for tonight include NPO after midnight. I know this means I should refrain from eating or drinking, but I decided to find out what the letters actually stand for:  Nil Per Os. That’s latin, but I’ll take a wild guess that it does in fact mean nothing by mouth (or NBM in english!).

Tomorrow’s date is 12/12/12. There will be more than the average number of weddings, induced labors (who doesn’t want a lucky baby) and lottery tickets purchased as well. I like to think it is an auspicious date. But it seems I almost blew it; my go-to-biopsy outfit was to be some black yoga pants. However, according to numerologist Swetta Jumaani in an article from the NY Daily News, “Black is a very inauspicious color,”……. “Something bad always happens.”

Out with the black, in with something colorful and not unlucky.

Me again

I would like to thank all my friends from INSPIRE for sharing your individual stories. I believe by speaking out you are empowering not just yourselves, but others who have been impacted by this devastating disease, lung cancer.

Now it’s time to update my own status.

I met with various members of my team last Wednesday. Due for a scan in two weeks, they bumped it up to that day after I described my growing anxiety over steadily worsening symptoms; cough, fatigue, and bronchorrhea.

Bronchorrhea is an uncommon symptom associated with the variant of lung cancer I have, mucinous bronchioalveolar carcinoma, and it is making bedtime miserable. The moment I lay down, my lungs start to crackle. For the next 30-40 minutes, I cough, hack and spit as I clear 2-3 ounces of frothy mucus from my windpipe. It is exhausting and at times frightening as well. There is no antidote for this sort of bronchorrhea, other than treating the underlying cause, the cancer itself.

Although some of my cancer is yet responding to treatment, it is likely that a new clone or mutation has been selected out for; one that is resistant to LDK378. This scenario is suggested by the appearance of my scans, as my cancer is returning in a very different pattern than it has previously. Rather than a gradual consolidation of diffuse nodules, much of what we are now seeing resembles billowing smoke, and is likely responsible for the bronchorrhea. However, the only way to confirm this hypothesis is to retrieve some cancerous tissue.

Fortunately, a biopsy is now considered doable and a core sample shall be removed from my left lung on 12/12/12. In addition, I will take my last dose of LDK378 on 12/11 and one week after the biospy, I will start chemotherapy; four rounds of Alimta/carboplatin followed by continuous maintenance with the Alimta alone.

When I underwent chemotherapy in 2005, I had a port installed. As it is a foreign body, there is a risk for infection and there are now a limited number of antibiotics that I can tolerate, so at least initially, I shall forgo the port. Should infusion through an IV prove too difficult, we will reconsider.

So that’s the scoop, from the medical perspective.

Six weeks notice

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This is day two of a week long visit from our twenty six year old son August. We hit the ground running yesterday, with a trip to Massachusetts General Hospital. David and Peter came along as well, and August got his first peek into this particular window of my life.

It turned out to be a bit much for him. A lack of geographical proximity has provided August with an emotional distance from my cancer; accompanying us on a visit to the hospital brought it all home, and shortly after we were shown to our private room, he broke down.

When Dr. Shaw came in, it was just David and myself. She asked some careful questions as to how I was feeling. Great, I said; heaps of energy and rock solid resolve. But when I lay down at night, the crackling/wheezing in my lungs was a potent reminder of where I was heading.

I had in fact just arrived: in clinical trial parlance, progression. Defined as (not 30%, as I stated in an earlier blog–now corrected) 20% progression from the nadir–or the least amount of measurable cancer in my lungs since starting trial. To break it down another way:  A positive response in a clinical trial is defined as a 30% or greater reduction in tumor burden. Ultimately, my cancer decreased in measurable area by 63% ; that was my personal nadir. My latest CT scan shows a 21.8% increase from that lowest point. However, I still have approximately 40% less cancer than when I started this trial.

My cancer is returning or progressing relatively slowly and I continue to maintain an exceptionally high performance status, (ability to complete daily tasks). If this were a standardized rather than experimental treatment, I would undoubtedly eke several more serviceable months from it.

As a participant in a clinical trial, I am bound by protocol (literally). Happily, Dr. Shaw pulled a rabbit out of the hat; Novartis has agreed to let me to stay on LDK378 for one more cycle. We now have six weeks to figure out where to turn next, and that softens the blow considerably. Soon, I will embark on a new adventure. In the meantime, life will be lived to the fullest.

After saying goodbye to Dr. Shaw, we collected the boys and grabbed a late lunch. Not deterred by the fact that it was already half past three, we continued on to Ipswich and Crane Beach.  Arriving just as the crowd for the day was thinning, we were met by clear skies and balmy weather. August and Peter took a quick dip in the chilly Atlantic and soaked up the late afternoon sun while David and I walked the length of the beach as the tide came in.

But we weren’t finished yet; August had requested dinner at the Clam Box, where the four of us worked our way through two enormous plates of fried clams.

Stuffed, but with much food for thought still on our plates, we headed home.

Time for a personal update

Now that it’s all over but the shouting, I can tell you that I am ever so happy that last week is history.

It had been an unsavory mix of constipation, infection, insomnia and liver toxicity. I felt awful, with a fever three nights running. Aches and chills, splitting headache, nausea and a total absence of appetite. On Tuesday, I started taking levaquin. On Wednesday, I had a chest CT scan and labwork:  my liver enzymes, which had been rock steady for weeks, were starting to climb. I was to stop LDK378 and levaquin both. Although exhausted, I never managed to sleep a wink that night; my mind going a million miles an hour. I have learned since that insomnia can be a side effect of levaquin, and in conjunction with nightmares, hallucinations and a host of other symptoms, a possible sign of a serious reaction.

Over the next two days my liver enzymes continued to rise, peaking at around ten times normal, although still significantly less elevated than the last go around with toxicity. I started on azithromycin for the chest infection and Thursday evening, after eight days without a bowel movement (which proved stubbornly resistant to both Miralax and glycerin suppositories), a prescription of lactulose finally did the trick. As tired as I was, I could have done a little jig. I also received this congratulatory email from my mother in law, with some advice should I ever find myself in such a ‘situation’ again:

Hallelujah(!) and (I’ll say it, so Kill me!) praise the Lord for Ducolax!  Could not believe what Dave reported about your recent days of pure hell.  My first thought was of the simple suppository (mum used to carve a wedge out of ivory soap to ease our blocks of cement to the Glory Land) but it seems that on this carefully controlled regimen, one cannot revert to old fashioned methods.  Not to digress, but to digress, John nearly died of croup several times as a young’n.  I remember many nights spent in a bathroom full of steam and, in the worst scenario, trips to the hospital at 90 miles an hour.  Then I heard that my Aunt Patty (mum’s sister), as a child, had croup as well, and once, during a severe bout when she was turning blue, Grampa Tripp dripped 2 drops of kerosene onto a sugar cube and fed it to little Aunt Patty.  It broke up the congestion and she resumed breathing!  This has nothing to do with what you’re going through, but it goes to prove there are times, when all else fails, Old Fashioned methods should not be dismissed.  When one has ingested food for 8 days and nothing is coming through the Glory Land, the troops have to resort to surprising the enemy from the rear.  It has worked in wars through the ages, and you, my Darling, are fighting a war.  I think you need me, my knife, and my ivory soap.

 I love you, mum

 P.S.  I have a whole box of rubber gloves left over from a few years ago…..

Today we returned to Boston to meet with Dr. Shaw, and my liver enzymes are trending down. Better yet, Dr. Shaw got the okay from Novartis for me to continue LDK at a dose of 400 mg once those enzymes have returned to normal– I had been certain I would only be allowed to go back on trial at a lower dose if at all. AND, the CT scan, aside from a new area in my right lung which likely represents infection, was STABLE. In fact, there is a “Slight decrease in ground glass opacity at the lateral left base…”

I really hadn’t expected the wealth of good news today, and in fact figured the focus would be on what therapy we would try next. I am thrilled that I will be allowed to stay on LDK378 longer, and happier still that my scans were stable.

Obviously, there will be no more sips of wine or outlaw margaritas, no more levaquin or NSAID’s. I’m going to focus on eating foods that are beneficial for the liver, and yesterday I had beets for breakfast, lunch and dinner. I’ve got some weight to gain back, and making sure I stay regular is a high priority.

My body sent me some powerful messages last week, and it got my full attention. I’m listening, and will continue to do so.

Results

I thank each and every one of you for the comments as well as the messages I received. My appointment yesterday was late in the day, and after arriving home around seven, I had a cup of tea and opened some emails. Too tapped out to write, I drew a hot bath and then went straight to bed.

David was out of the house early, so after driving Peter to school, I sat down at the computer and thought I better get a blog up. Alice called (bless her) with some measurements and clarification and then I decided that what I really wanted to do was go back to bed. And I did.

Morning naps are the best. I awakened rested and with that pleasant sense of momentary disorientation…still a bit tangled in the brief dreams I’d just had and totally free of yesterday’s worries.

So. The reports from the scan are not a catastrophe. What was characterized in the previous scan as ‘These findings may represent mild increase in minimally invasive adenocarcinoma‘ is now ‘Increasing round glass opacities in the lateral portion of the left lower lobe and slight interval enlargement of a nodule adjacent to the right minor fissure are suspicious for progressive lung cancer.

Simply put, it is clear that I am developing resistance to LDK378. My cancer, that tricky devil, has figured out a way around yet another therapy.  The largest single lesion, which is actually a patchy ground glass opacity, measured 2.5 cm at its longest point on 2/21/12 and was stable from previous reports. On 4/03/12, there was a slight increase to 2.8 cm. The latest report, dated 5/15/12, notes an increase to 3.5 cm.

Clinical trials utilize a tricky algorithm called RECIST to measure response. The technique is planar, rather than volumetric and is based on averages from several target lesions. BAC, which is characterized by hazy infiltrates rather than clearly delineated solid tumors, is not given to easy quantification.

As Alice explained this morning, for the purpose of the clinical trial, my tumors are only minimally increased in size. This is important, because after a certain degree of progression has occurred, a participant will likely be asked to leave the trial.

That’s the good news. The bad news is that the cows are out of the barn and although not yet stampeding, they are getting mighty restless.

So what’s next? Stay the course for the moment. Inquire as to whether or not Novartis would grant permission to return to a dose of 500 mg LDK once again; albeit with careful monitoring of liver enzymes. Monitor my physical symptoms closely; there is in fact a bit of wheezing in both lungs now.

We will also watch that 6 mm spot in my right lung with interest; perhaps it might become a candidate for biopsy whereas the ground glass opacities are fairly useless in that respect. A curious aspect of this particular recurrence is that although the cancer is cropping up in pretty much the same spot it has before, the appearance is slightly different; more haze and less opacity. And that 6 mm nodule appears to be an entirely different beast altogether, prompting me to ask Alice if it is possible that these two separate areas of apparent progression might be driven by individual (and newly acquired) mutations, each conferring their own mode of resistance. Intriguingly, but damnably frustrating as well, the answer is yes, that is possible.

In conclusion, I started on LDK back in September of 2011. Nine months and counting for an experimental cancer treatment is really quite good, and I knew when I signed on, that this would be a temporary fix. I hope to squeeze another few months out of it but if that’s not possible, there are options. Which in itself, is an amazing thing.

I told Alice yesterday that I’m planning on attending Peter’s graduation from high school. That will be three years from now. She thinks it could be doable.

That’s all I need to hear.

Exhibit A (ALK+)

By last weekend my GI tract had returned to what now passes for normal, and I was ready to get back in the game. Pete shipped up north for a dance at his former school and then on to a friend’s house, and Melinda and Kihan joined us for the grown-up version of a sleepover. At dinner my companions went through several bottles of fine wine; I teetotaled.  On Easter Sunday we scooped up Peter and the five of us went to brunch. Aside from that repast and the giant Easter Basket Melinda assembled for Pete, the holiday would have come and gone without much fanfare. End of an era it would seem; no more egg dyeing, stuffing (the plastic kind) and stashing for the hunt. Should any of our progeny produce grandkids, perhaps we will revisit these activities.

Monday I drove to Boston for my scan review, and was able to grab some time with my friend Ginger beforehand. It is always lovely to see her, and we must do it more often!

At the appointment, Alice (Dr.Shaw) showed me the most recent scans side by side with the ones from February. Overall, there is no significant increase in size of nodules, and the activity in my right lung remains remarkably stable. Unfortunately, what remains of my left lung, the scene of the original crime, is a bit of a trouble maker. The radiologist who read these scans is very thorough, and the report is lengthy and replete with detail. To wit (not even the complete report):

“There is a mixed solid ground glass opacity in the peripheral left upper lobe beginning on image number 60 extending through image number 67. This is increased in density when compared to the prior examination. …there is mild increase in ground glass opacity in the lingula adjacent to the pericardium in images 71 and 72. There is a region of increased ground glass opacity in image number 76…there is some increase in ground glass opacity adjacent to the left ventricle on image number 91 and 95…when comparing to the examination of November 2011, the mixed attenuation lesion in image number 65 is increased in size and density. The ground glass opacity in the inferior lingula has also increased.”

Lotta lotta ground glass being tossed around. However, the final impression is:  “These findings may represent mild increase in minimally invasive adenocarcinoma in these regions”. Minimally invasive adenocarcinoma is the new term for BAC, or broncioaveolar carcinoma. I have some quarrels with this change in nomenclature, but that is for another blog.

At any rate, the areas of greater consolidation mean that I am no longer stable. However, particularly viewing the scans, which didn’t look that bad, I feel it was yet a good report. Aside from my three week respite with the hepatotoxicity, I have been on LDK since September 7th, 2011, and I believe I’m going to get a lot more mileage out of this particular therapy.

Tuesday I returned to Boston for a double header of sorts. I finally had the opportunity to meet my friend Craig, who is ROS1 positive and on trial at MGH as well. Craig has written a great deal about his own experience on Inspire, the online support group we both belong to, and at my urging, he will soon do some guest blogs here as well.

Following his appointment, Craig joined me for the opening ceremony of the Paul S. Russell Museum of Medical History and Innovation at Massachusetts General Hospital. Doctor Russell and Boston’s own Mayor Menino cut the ceremonial ribbon (actually high tech gauze), after selecting their tools of choice from an array of surgical implements borrowed from the museum’s collection.

My claim to pride of place at the ceremony was due to the fact that some video footage of myself and three other individuals–one of whom is my friend Greg, appears in an exhibit showcasing the use of targeted therapies at MGH. And now, for my best ‘I’m part of a museum exhibit’ smile:

If you are interested (my moms never get tired of this stuff), here is a link to some related content as well as the original video.