Tag Archives: LDK378

Viewing the actual scans

I had my appointment with Alice (Dr. Shaw) on Monday, and we were able to view the images of the before and after scans together. They do indeed appear much improved. In my left lung, there remains a hazy footprint of what was formerly an area of consolidation. It could represent inflammation or, possibly more likely, unresolved cancer. The right lung (my ‘good’ lung), looks almost entirely clear.

It is important to remember at this point that A. we are in the dose escalation phase for LDK378, and the therapeutic dose may not have been reached yet, and B. this is not my first exposure to an ALK inhibitor and my cancer had acquired resistance to crizotinib (Xalkori).

All in all–a very respectable response. We will be watching my next set of scans closely and also positioning for dose escalation as soon as possible (there are certain constraints per protocol–and it will be six weeks or so before escalation is a feasibility). Update–Alice received the measurements for resolution (which is factored in a way that is very reliant on degree changes in borders of tumor rather than density) and it is 19%. This is a good place to remind all that I learned a long time ago not to be defined by numbers. I prefer qualitative to quantitative analysis, and symptomatically, I am much improved.

Life goes on. I’ve been busy adding to my portfolio of fallen leaves, although it has not been a stellar season for leaf peeping. They take the fall colors quite seriously in these parts, and there was a story on the front page of the local paper detailing the factors behind the disappointing showing. A very wet spring, coal tar spot, hurricane Irene (which atomized so much salt, it was found on the leaves of maples twenty miles inland). I believe myself to be rather adept at finding something beautiful under any circumstance though, so here goes:

YES! The results of the latest scan are in

I have been feeling well for the past week. My cough has resolved, my energy is up and the chills are gone. All good signs.

This past Monday I underwent the bronchoscopy. Quite uneventful aside from the nasty numbing stuff they squirt up your nose and down your throat prior to the exam. “This is going to feel like you’re drowning” counseled the attending nurse with no apparent irony. And it did.

On Thursday I was back in Boston for my chest CT scan. Although I’d been given a bye on barium for the past two years of the crizotinib trial, I am once again required to drink two ‘milkshakes’. As I’ve explained in some previous detail, I am oblivious to most of the discomforts involved in my day to day medical care. You don’t even want to know how many times I get jabbed with a needle. However, I have never liked putting something in my mouth that I don’t want there. I am, in fact, almost phobic in this regard. Oral contrast is tough for me, and hopefully I can once again talk upper management out of the necessity of such an (onerous) detail.

I had taken the bus in, and David picked me up at the hospital after my exam and we continued on to Randolph, where my oncologist, Dr. Alice Shaw, was being honored by the American Lung Association. Also in attendance were three of Alice’s other patients, including Chris and his wife Karen, pictured on the rather dramatic staircase of the venue. They have an adorable daughter who is just two, and Chris has done quite well on crizotinib. I wish him many more years of success.

Chris and Karen

Bright and early yesterday morning, Alice called and said she had reviewed the scans and that they looked really good, and as well the bronchoscopy was completely negative for any findings. Some hours later she forwarded the CT report, which frankly sounds even more positive than what I’d expected from her description. It reads:

FINDINGS:

Lines/tubes: None. Lungs and Airways: There is improved consolidation in the left upper lobe and lingula with residual ground-glass opacities, which had been previously chronic and progressive and are considerably improved from 8/31/2011, consistent with improvement in lymphangitic carcinomatosis.

There is a stable 3-mm nodule along the minor fissure. The surrounding smaller nodules have resolved. Pleura: There is a stable small left pleural effusion.

Heart and mediastinum: The thyroid gland is normal. No significant mediastinal, hilar or axillary lymphadenopathy is seen. The heart and pericardium are within normal limits. There is mild pericardial thickening, which appears more prominent compared to 8/31/2011.

IMPRESSION:

History of non-small cell lung cancer status post left lower lobectomy. Improvement in lymphangitic tumor spread in the left lung. Stable indeterminate 3-mm nodule along the minor fissure. Slightly increased mild pericardial thickening.

I like how many times improved or a variation thereof is used in the first paragraph (three), and the addition of considerably is even better. Stable appears twice in the second paragraph. And in IMPRESSIONS, the key words are improvement, stable, and slightly increased. This is a very good, considerably improved, report. Yippee!

And now for some definitions of less than familiar terms:

lymphangitic carcinomatosis:  A condition in which cancer cells spread from the original (primary) tumor and invade lymph vessels (thin tubes that carry lymph and white blood cells through the body’s lymph system).

This is the definition from the National Cancer Institutes online dictionary. From Medscape reference we get this explanation:  The lungs are one of the most common targets for metastatic disease.  Most pulmonary metastases are nodular, but a significant minority is interstitial. Lymphangitic carcinomatosis (LC) refers to the diffuse infiltration and obstruction of pulmonary parenchymal lymphatic channels by tumor.

Interpretation? I believe it is simply another way to describe metastatic lung cancer.

I also looked up the significance off mild pericardial thickening (the pericardium is the membranous sac enclosing the heart), and will discuss it with Alice before I attempt to interpret this finding.

Bottom line; it is a very good report. I have to wonder if I really did have an infection that the latest course of levaquin vanquished. Whatever the underlying cause of my initial malaise as well as the less than stellar PET scan, it is now evident that the LDK378 is having it’s way with my cancer. I’m tripping over myself with gratitude, and well, excitement. The personal impact is obvious, but I’m focusing on the big picture as well; perhaps LDK378 will prove to be yet another viable treatment option for those who harbor an ALK mutation. That would be really be something.

well

Darkness falls earlier and the leaves are turning. Already bursts of color litter the forest floor; soon it will be an almost fantastical carpet of yellow, pink, red, orange and purple. I have begun my daily treks, camera in hand, attempting to capture…

I feel as if some seasonal change is taking place for me as well.

This is not easy to acknowledge, but I had, beyond merely hope, almost an expectation  in regard to this current clinical trial. I visualized myself having a rapid response and returning, once again, to a period of good health. While on crizotinib, my lung cancer had seemingly melted away. This time, a model of my new mutation had been tested in the lab and shown great sensitivity to LDK378.

On Friday I had a PET scan to assess my progress thus far. The report read:

FINDINGS:

Overall mild decrease in size of intensity of uptake in opacities in the bilateral, left greater than right, lungs. No abnormal foci of  uptake are identified in the mediastinum. No other abnormal foci of uptake are identified.

IMPRESSION:

Mild interval decrease in bilateral lung tumor burden.

It is not a negative report. Nor does it indicate any sort of rapid response to the trial drug.

First, an explanation of what a PET scan is and does. PET is an acronym for positive emission tomography, and, as defined by Wikipedia:

“Positron emission tomography (PET) is a nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emittingradionuclide (tracer), which is introduced into the body on a biologically active molecule. Three-dimensional images of tracer concentration within the body are then constructed by computer analysis.”

“If the biologically active molecule chosen for PET is FDG, an analogue of glucose, the concentrations of tracer imaged then give tissue metabolic activity, in terms of regional glucose uptake.”

My PET scan before I started the trial was somewhat ‘hot’, meaning my lungs showed an ‘avidity’ (uptake of) the FDG-PET  (2-deoxy-2[F-18]fluoro-D-glucose positron emission tomography). 

The histology of my lung cancer is BAC, which generally shows only mild FDG avidity.

So what is going on here? There are several possible answers. A PET scan essentially measures metabolic activity, the theory being that a highly metabolic area shows a greater avidity (or eagerness) for glucose. Neoplasms tend to be highly metabolic. However, several sources of inflammation could also produce these ‘hot’ spots. Perhaps I have an unresolved pneumonia which is showing partial resistance to the levaquin. I did feel much better when I was taking the antibiotics.

It may be that my cancer itself has ‘heated up’ or become more metabolic and therefore more aggressive, potentially transitioning away from pure BAC to a histology more in line with adenocarcinoma. Or, despite the early promise, LDK378 may be working, but potentially not as well as we’d hoped.

A passage from the archives of GRACE (an excellent online resource):

“Dr. West: In the metastatic setting for lung cancer specifically, clinical trials include CT scans to assess response or progression.  Do you believe that the PET scan adds significantly to that or can we do as well with CT scans basically showing shrinkage or enlargement of known disease? 

Dr. Djang: Definitely the PET scan has been proven to be more accurate in the setting of metastatic disease.  I think what it comes down to is that if the treatment is working, if the chemotherapy, chemoradiation therapy is working, the first change that you’re going to see is a decrease in the metabolic activity of the tumor cells.  That can only be measured with a PET scan and that change will come first.  The CT can only measure response to therapy by looking at tumor size.  That takes time.  It takes time, at least some time for a tumor to grow or to shrink if the therapy is successful.  If you have a car that has stopped running, the engine will become cool long before the body of the car starts to degrade.  So in the same concept, the metastatic deposit will cool off on the PET scan before it shrinks.  

Dr. West: So a PET scan may be especially valuable in getting some early feedback about whether your treatment is likely to be helpful or not? 

Dr. Djang: Early and more accurate, yes.” 

It has not been an easy time to stay hopeful. I have several friends who are struggling with their disease and I don’t know what the hell is going on with mine. Some weeks ago a post I had written for my online support group  regarding battle fatigue was republished on e-patients.net. I concluded it on a strong note.

I started on levaquin again yesterday; just so that I can feel better. Tomorrow, after my labs, I’m heading to NYC for a few days with my dear W & C. Next Monday I am scheduled for a bronchoscopy. Not only will the surgeon ‘harvest’ some fluid for a culture, an enlarged lymph node might be biopsied. And then on Thursday I will have  a chest CT scan, which is an anatomic versus metabolic view of my disease.

My desire to think positive is sometimes subjugated to my need to think possible; as in all possible outcomes. To prepare myself for whatever comes. But if you spend too much trying to see what lies ahead, you may miss the very moment.

Let me introduce: Evan

Picture taken of my girlfriend (Anne) and I in Vail. March 2010.

My name is Evan Spirito. I am 24 years old and I have NSCLC driven by a mutation in my ALK gene. I was diagnosed in January of 2009 when I was 21.

The cancer originated in my left lung and, by the time I was diagnosed, it spread to my lymph nodes as well as a couple brain metastases. I had the brain mets “zapped” right away with proton beam radiation and then I started chemotherapy. I experienced good results on the Patel Regimen (Carboplatin/Alimta/Avastin) for 6 cycles and then remained on maintenance chemo for several months following. Unfortunately, my cancer started to come back in the spring of 2010.

The results of my genetic testing came back in the meantime and confirmed that my cancer was driven by the ALK mutation. I was put on the Crizotinib trial and again experienced good results with very little side effects. I stayed on the trial for about a year before my cancer once again showed progression in the spring (March 2011).

I started on the STA9090 trial next, however, it proved to be largely ineffective on my disease with the addition of nearly intolerable side effects. After about a month “wash out” period, I began my latest and current trial (LDK 378).

Linnea and I share the same oncologist (Dr. Shaw). She reached out to me a few weeks ago and we discovered that we had quite similar experiences/treatments in our individual battles with cancer. Linnea was about to start the LDK trial herself and, as far as I know, we are two of only a handful of patients currently on the trial.

I know that the many patients are hoping to join the trial soon and looking for more information on what to expect, so, I wanted to share my experience thus far on the LDK trial:

The trial is comparable to my experience on Crizotinib, which was the best/easiest treatment I’ve had to date. The first couple visits are quite long (as Linnea described in her latest post) but after that it gets better. You will dose once a day and go in once a week for lab work and a check up. I have not seen any noticeable side effects from taking the pill apart from one vomited dose in the first week.

For me, the most annoying part of the trial is the eating requirements. Fasting for 2hrs before and after dosing is no fun but if you work out a consistent schedule it will not be an issue. I tried, and may try again, dosing right when I woke up (before eating), then going back to bed for 2hrs before eating breakfast. If your stomach can manage, it might be worth a try.

In my case, it took a solid 7-10 days before I really began to feel the pill working. Sure enough, my first set of scans revealed a major decrease in my disease, which is very encouraging. Things were going rather smoothly until I suffered a minor set back in the form of a chest infection, but with any luck the antibiotics should take care of that and hopefully I’ll be back on track in another week or so.

While being treated for the infection, Dr. Shaw did notice “slight progression” in my disease; however, not enough to take me off the LDK trial. So, as of right now I will continue with the trial for as long as its continues to keep the cancer down.

I hope this little bit of information helps but I’m also aware that every situation is different. As always, take it one day at a time, focus on what’s important going forward, believe in the treatment and it will work!

Evan is an incredibly brave and strong young man (yes, you can get lung cancer when you are only twenty-one).  As the LDK378 trial is yet so nascent, there is very little in the way of anecdotal informational provided by actual participants.  He was kind enough not only to agree to meet me but to generously share his own experience thus far here. Hopefully it will prove useful to other ALK ‘mutants’ who may be considering the LDK trial.

Thanks Evan!

Let’s ride

Ok. So. About that LDK378 trial…The gallery above is from my first day two weeks ago. Please note the woodchuck.  And Sarah, giving me the high five after my lead-in dose.  And how tired David looks; it was a very long day. Long enough that I had time to wander the halls, peruse the Wall of Hope and hang out in the lovely Healing Garden. Long enough that it was barely light when we left the house and quite dark when we returned home.

I’m going to directly lift from the Research Consent Form (a many paged document that you must read and sign prior to enrollment in a trial) to describe the specifics of day one:

PK run-in period (3days) in Part 1 of the study 

Pharmacokinetics (PK) is the study of the actions of a drug in the body over a period of time (eg, how it is absorbed, distributed, broken down, and excreted).

The PK run-in is a 3 day period (before you begin daily study treatment with LDK378) where you will be given a single dose of LDK378 and then have repeated blood tests to see how your body handles the drug. (The tests are called pharmacokinetics or PK tests.) About 1/3 teaspoon of blood with be drawn at each PK blood draw.

  • Day one of PK run-in:  You will have blood drawn, take one dose of LDK378, and then have blood drawn 7 more times with the 8 hours after taking LDK378.
  • Procedures performed on Day 1 of the PK run-in:
  • Physical examination
  • Vital signs
  • In addition, blood pressure and heart rate will be measured before every PK blood sample is drawn.
  • 3 consecutive  EKGS after the single dose of LDK378 and another EKG 4 hours after the dose of LDK378.
  • Additional blood for research blood test to measure biomarkers and the amount of circulating tumor cells in your blood (about 4 teaspoons). Biomarkers are substances such as proteins that may give information about how LDK378 is affecting your body.

So that is the technical run-down. In reality, it all felt rather festive.  Just as my t-shirt proclaimed, this wasn’t my first rodeo and I kind of knew what to expect. 

Not long after the first dose, I experienced some cramping and Irene performed anti-diarrhea acupuncture. That was it for drama; no other discernible side effects. 

Wouldn’t it be wonderful if my personal history of lung cancer treatments someday represented the paradigm; thus far, they have only gotten easier and become more effective.

Consider: almost immediately following my diagnosis in 2005, I endured a rather brutal lower left lobectomy. That was followed by four grueling sessions of cisplatin and taxotere. In 2008 I spent two months taking tarceva with all of the side effects and none of the benefits.

And then came crizotinib (now Xalkori). Not only were the side effects minimal, it stamped out the cancer raging in my lungs and kept it at a low smolder for almost three years.

Will the LDK378 do the same? I am hopeful. The day after my lead-in dose, I was able to walk to the top of a steep hill without stopping numerous times to catch my breath; something I’d not been able to do for some time now. I felt great.

And then, I started to feel crappy again. Which is part of why I haven’t written yet.

However, before any conclusions are leapt to, I need to add that there were several extenuating circumstances. Two weeks before my lead-in dose, I had been on a ten day course of levaquin for a sinus infection. It was the first time I’d had antibiotics in months, and a curious thing happened.

The cough and accompanying rattle in my lungs, which had persisted almost since my bout with the flu, disappeared. I had assumed both symptoms were due to the progression of my lung cancer and was actually quite startled when they cleared up.

My lead-in dose was on a Wednesday, and I didn’t have another dose (the start of continual dosing) until the following Monday. In the meantime, the feeling of low level crappy returned; aches, chills, fatigue and a cough. What the hey!

Several months ago I found an imbedded deer tick but in subsequent days did not develop a bullseye rash. However, just to rule out lymes disease as a potential cause of my current symptoms, I was tested. In addition, my circulating hormone levels and thyroid were checked; all three were normal. Alice (Dr. Shaw) called on Sunday to see how I was feeling and mentioned that the pre trial PET scan had shown more uptake in my lungs than she had anticipated.We discussed the possibility of a smoldering low level pneumonia, as areas of inflammation can light up a PET scan and be confused with cancer. Finally, yesterday I saw the ENT to rule out a lingering sinus infection. My nasal passages were clear, but we decided it might be smart to go back on another ten days of levaquin and see what happens.

So here’s hoping. The side effects from the LDK378 would seem to be non-existent. If the antibiotics do their magic, perhaps I can really get back in the saddle again. I am so ready.