Tag Archives: LDK 378

The downstream effect of two miracles of science

Posted on October 12, 2016 | 10 comments

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

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Posted in Advocacy, ALK mutations, LDK 378

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Exhibit A (ALK+)

Posted on April 12, 2012 | 8 comments

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.

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Posted in LDK 378

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The numbers look good

Posted on March 6, 2012 | 38 comments

I have a newly developed and profound sense of respect for my liver. The AST/SGOT is down to 53 (normal range is 7-30) and my ALT(SGOT) is 43 (normal range is 9-32). This constitutes a mild but entirely acceptable level of inflammation/irritation; the insult and injury has been forgiven. I savored my final grapefruit on Thursday of last week, and last night I started back on LDK 378 at 400 mg.

I experienced a small amount of cramping post dose and felt enough fatigue that I took a nap after breakfast this morning, but all in all, it is an uneventful rechallenge thus far. On Thursday I will have my liver enzymes checked at the local lab; to do so is not mandated by trial protocol, but both Dr. Shaw and I will feel better not waiting until next Monday for my weekly blood draw.

Better yet, Alice (Dr. Shaw) called with some additional news this morning. My tumor response from the last chest CT scan had again been reevaluated, and it has jumped from 45% to 62.4%, which is approaching the phenomenal c 70% I experienced on crizotinib. Now that’s what I call a sweet vote of confidence, or as Mary Poppins might say, ‘just a spoonful of sugar helps the medicine go down.”

Cancer, your little vacation is over. We’re back on track.

 

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Just desserts

Posted on February 28, 2012 | 17 comments

One more week off drug. My enzymes continue their descent, with the AST/SGOT now in the realm of normal with a value of 41 and the ALT/SGPT at 100. It’s the ALT that needs to come down more, but the team is confident that I’ll be there by next Monday. The plan is to rechallenge with LDK 378 at a lower dose of 400 mg (the original dose at which I entered the trial).

Just as Dr. Shaw predicted, the radiology report from my scan reads:  “No significant change in patchy groundglass opacities and mixed attenuation lesion in the left lung, likely corresponding to lung cancer. Stable two 5mm nodules in the right lung. Interlobular septal thickening in the posterior left upper lobe unchanged, likely represent(ing) lymphangitic carcinomatosis. Stable small pleural effusion.”

Lots of stables and a sprinkling of likely as well–likely connoting a pleasing if unlikely lack of certainty. I’ll just run with it…

I am just about done with the course of antibiotics and I feel the infection has cleared up. However, I am experiencing some new shortness of breath and  Alice (Dr. Shaw) confirmed a wheeze in my left lung. Trouble maker, that one (the lung, not Alice). I’d like to believe I’ve just fallen out of shape as I’ve not been walking the past two weeks. I did ask about the possibility of a flare in my cancer while I’m off drug; a phenomenon that has been document in the wash out period for patients coming off tyrosine kinase inhibitors (targeted therapy for EGFR positive cancers). The answer was yes, it is possible but, she felt, unlikely. I can’t help myself. Some people are more comfortable with less information, some of us want to hear it all; the good, the bad and the ugly.

But, there is one very bright if momentary spot of sunshine. Grapefruit. I adore this particular citrus, and I hadn’t had one for four years. Grapefruit can interact in a potentially dangerous fashion with several cancer therapies and therefore is verboten. A week ago we received a bushel of oranges and grapefruit from David’s employer. This time, I didn’t have to look on with envy but could partake. Woohoo!

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A bit too close to the edge

Posted on February 23, 2012 | 17 comments

I get my feet wet

I was discharged Sunday. Six pounds lighter and pretty darn worn out after my adventure, but happy to be home. I am back on the antibiotic levaquin, my persistent cough is finally abating and David has made the feeding and fattening of Linnea his pet project.

On Tuesday I returned to Boston for labs, a CT scan and to meet with Dr. Shaw. My ALT/AST are continuing to come down, but are still elevated. The LDK 378 will be held for another week and I will have labs on Friday and again on Monday to make sure the downward trend continues. Although I don’t have the radiologist’s report yet, Dr. Shaw reviewed the scans and feels that the activity in my lungs is at the very least stable, and at the very best, maybe even slightly improved.

All of the tests for outside causes have been coming back negative, as anticipated. When I said I was being test for Hepatitis, I should have specified viral Hepatitis. I have learned that hepatitis is a generic term for liver injury and inflammation. Drug induced hepatotoxicity (pronounced (hep′ă-tō-tok-sis′i-tē), and referring to the capacity of a drug or other agent to induce liver injury) is also referred to by the acronym DILI or drug induced liver injury. It is relatively uncommon, “DILI in the case of any single drug is thought to occur approximately in one per 10 000–100 000 treated patients.”  (from Pub Med Central). However, I wonder if that statistic is pertinent to clinical trials. Phase I of a trial, such as the one I am enrolled in, is to determine at what level a drug can safely be administered, and to do so through dose escalation. Although my ALT/AST were significantly elevated, the fact that my liver function was never compromised is an important distinction, not just for me but for the the trial itself. Severe DILI is defined as liver failure or death, two bullets I obviously dodged. However, it would seem that the careful monitoring I received was not misplaced, as evidenced by this article in Medscape about drug induced hepatitis.

Although I would like to go back on trial as soon as possible, I have some trepidation as well. There is the possibility that when the LDK 378 is reintroduced, the scenario may be repeated. Of course, the only way to find out is to try, and I assume I would be monitored even more closely at rechallenge (the opposite of dechallenge, or holding of the drug).  The FDA has published a Guideline For Industry that specifically addresses the issues surrounding DILI in a clinical trial setting, should you be interested in the specifics.

In the big picture, it is not so very important, but I’m sad to say that my drinking days might be over; I can’t even look at a glass of wine anymore. And I had such a talent for (the wine tasting) and sublime appreciation of. Oh well. I actually awakened in a bit of a cold sweat last night because I dreamt I’d had a cocktail.

So, in conclusion, I came out on the good end of a bad week. I am both highly encouraged and deeply anxious about where we go from here. And I will keep you posted.

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One two punch: medical and emotional update

Posted on February 16, 2012 | 27 comments

First to the heart, and then to the gut. Last Thursday, undone by the passing of yet another friend, I was given the go ahead to get back on prozac. I’d made it four months without chemical support and the decision to return to an antidepressant was not made lightly. I had become such a cry baby and it was beginning to feel untenable. I may be strong, I may be brave (most of the time) but I suck at sad.

By the weekend, it was clear that the tickle in my chest had bigger plans. Come Sunday I was feeling plenty sick with a chest/sinus infection. On Monday I was at MGH for labs, and asked to see a nurse. I knew I’d need an antibiotic, but the LDK 378 is an occasional challenge for my gastrointestinal track and in December I’d taken a single 750 mg tablet of Levaquin to rather disastrous results.  I was concerned about what havoc a full course of antibiotics might wreak.

My sodium was trending low and in anticipation of some GI disturbances we talked about the possibility of an IV boost. She got me a sputum cup for a culture. But then my liver enzymes came back and the levels were significantly higher than they had been a week ago. My lactic dehydrogenase (LDH), an indicator of inflammation, was also elevated.

Game plan changed. The degree of liver enzyme elevation I had (greater than ten times normal) constitutes a grade 3 event in a clinical trial. Dr. Shaw joined us and explained that I would need to go off drug, at least until my enzymes came down.

It’s called a drug holiday, but not as much fun as it sounds.

I am on a lower than my usual dose of Levaquin (500mg) for the chest and sinus infection. There is a chance that the addition of fluoxetine (prozac) mitigated the dramatic fluctuation. The thought was to stay on prozac and see if my levels came down. On Tuesday, really feeling lousy, my appetite nowhere to be found, I decided that I would just stop taking it. If a boat is taking on water, you throw everything that is not essential over the side.

Today I  had lab work done locally. My hope is that the levels are receding; if they should come down enough I could start back on trial in a week. If they haven’t, than it may be that something other than the trial drug or the prozac is causing the elevation. Had I stayed on the prozac, it obviously would have made it easier to rule out the trial drug, but I just wasn’t willing to do that. Next Tuesday I have more labs, a CT scan and a previously unscheduled chat with Dr. Shaw to see where we’re at with all this.

In the meantime, I’m resting a lot, eating what I can (David is a great pusher of food) and crossing my fingers that this is just a bump in the road.

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Saddle up

Posted on September 11, 2011 | 9 comments

THIS AIN'T MY FIRST RODEO

 

Wednesday morning, September 7th. Lead in dose of LDK 378 and dressed for success.

It was a long day (eleven hours not including the commute), but went quite well. Per trial protocol, I returned to MGH Thursday, Friday and Saturday morning for PK’s and blood draws. After a day off, I’ll be back again bright and early tomorrow to begin regular dosing.

I’m going to fill in the blanks, but not tonight. This tuckered cowboy is hitting the sack.

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Posted in clinical trial, Treatment

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FDA approval for crizotinib and a new name: Xalkori

Posted on September 1, 2011 | 33 comments

On Friday, August 26th; crizotinib received FDA approval. It is now called Xalkori. Nice little features on both the ABC  (scroll down to find Xalkori) and NBC evening news a couple of nights ago. That’s my oncologist/goddess Dr. Alice Shaw providing commentary, and in the NBC piece, the images of the before and after chest CT scans are my lungs (an online friend recognized them and emailed me!). They do get around (my lungs and Alice).

I should also mention that there was a story about Pfizer’s coup in the Wall Street Journal on Tuesday with a picture of and a few quotes from yours truly. My Dad Ollie, who read the WSJ faithfully, would have been pleased to see me there.

I’ve noticed some criticism on the blogsphere, as Xalkori comes with a hefty monthly price tag ($9600), but Pfizer has taken steps to provide financial aid for those who need it. Also called out has been the fact that only 4-6% (or according to this latest data, almost 10%) of people with NSCLC have a mutation of the ALK gene. However, there are so many cases of lung cancer world wide (according to WHO, 1.4 million deaths yearly from lung cancer), that when you do the math, it is a truly significant number of patients who shall potentially benefit.

So yes, Xalcori is big news for Pfizer as well as those of us with lung cancer and the FDA is to be applauded for streamlining the often ponderous approval process.

And now, on a more personal level; what’s up with me.

On August 19th I took my final dose of crizotinib (Xalkori). I am now ‘washing out’ in preparation for my next party trick (make that a miracle). Yesterday I peed in a cup, had bloodwork, a physical, an EKG, a chest and abdominal CT (with contrast–blech) and a PET scan as well. I was given one of those nifty cards identifying me as residually radioactive for 24 hours (just in case I encountered someone with a geiger counter).

I am scheduled for my lead in dose of LDK378 next Wednesday and that’s when the circus really starts.

In the meantime, I am feeling pretty crappy. I saw Alice (Dr. Shaw) yesterday, and she thinks that quite probably, the crizotinib was still conferring some protection, which is good news if in the future we want to add it to my arsenal again. Now that I’m off treatment, my energy level has really dipped and my shortness of breath is catching up to me. Today I made myself go on a walk, as I’ve been breaking my own rules lately (never stop moving). It was also Peter’s first day at the Academy, and he’s going to require a lot of support as he adjusts to a very rigorous academic schedule, so I’ve got to stay on my toes.

What can I say? It is a stressful time for all of us, but we are doing our best to stay positive and hopeful. Because that’s how it’s got to be.

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Posted in clinical trial, genetic testing, Media, personalized cancer care, targeted therapies

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A scan and a plan; but first, a tribute

Posted on July 16, 2011 | 25 comments

I had a message from Beryl, Guillermo’s wife, this morning. Guillermo Berazadi passed away on Wednesday morning July 13th. His wife and two daughters were by his side.

Although I have known for several weeks that this was an inevitable conclusion, I am beside myself.

Guillermo’s first contact with me was ‘I like your blog and I like you’. It was mutual, as I fell in love with this man of insatiable curiosity, humor, and zest for life. Guillermo’s comments were little novellas, and as he shared his own remarkable story, Gil built a devoted following. When he was silent for too long, I would receive personal emails inquiring as to his well being. I would then harass him (he like playing hard to get sometimes) until he burst forth with some fresh brilliance.

I am glad Guillermo is no longer in pain, but I shall miss him so. My life has been made richer by his friendship. I take comfort from the wise words of Stephanie (a member of the Guillermo fan club):

“G – as always, believe there is solid ground beneath us or that we learn to fly as we take that next step.”

Rest in peace, my friend.

And now, my own update.
Slight further progression compared to my scan of two months ago, however, rather significant progression in general. In other words, slow but steady.

As Alice (Dr.Shaw) said; she would have preferred stability, (oh hell, let’s just go for remission), but at least it’s not galloping. And, we now have a menu of options.

As my performance level is still very good, Alice would like to keep me on crizotinib until we know that it will receive FDA approval (for which it is currently being fast-tracked) that way, should other treatments fail, I have the option of returning to crizotinib (as it would seem to yet confer a partial response).

Once approval is certain, I would get in queue for a trial of Novartis’ LDK 378, the first second generation ALK inhibitor. LDK 378 is administered in tablet form, is a very selective inhibitor and exhibits five times the potency of crizotinib. In addition, a model of my mutation in the lab (from the cell line started with material from my last biopsy) was sensitive to this particular ALK inhibitor. So, it is very promising.

Another experimental drug from Novartis, AUY922, an HSP-90 inhibitor, remains an option as well, but would involve weekly infusions and possibly broader side effects. Although not specific to ALK mutations, my  secondary mutation model again showed sensitivity to this particular HSP-90 inhibitor in the lab.

So, on the one hand I am sad to be going down this path again, but I am also mindful of the fact that this time I have a compass, a map and Dr. Shaw by my side.

I will close today’s blog with some photos from an excursion I undertook last weekend with my friend Julia, to Strawberry Banke in Portsmouth NH. We had a wonderful time and I was much taken with one of the displays; an old home preserved in a marvelous state of decay. Just a reminder that there is beauty everywhere, every day, no matter what.

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Posted in ALK mutations, Death and dying, Living with lung cancer

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