On Tuesday night, November 10th, ABC World News aired a story that was a follow-up to their June 2nd, 2009 report on personalized cancer care. Tuesday’s report featured Bill Shuette, the gentleman I had the pleasure of meeting last week. Click here to see the report. When the story about my response to PF-02341066 aired in June, there was a flurry of interest in this new “wonder” drug. Many people were disappointed that this treatment was not the answer for them or their loved ones. However, for a handful of people, it was indeed a lifesaver. Bill is among them.
Once again, message boards are heating up with interest, and I would presume that MGH and other facilities that are sponsoring the third phase of the PF-02341066 trial will field many phone calls. As the ALK mutation occurs in a minority of lung cancer patients (3-7% of lung cancers, adjusted up to c. 13% for light to never-smokers), this treatment will not be appropriate for the majority. However, I have no doubt it will prove a godsend to some.
Traffic on my blog was much heavier yesterday, with many people logging on to read about PF-02341066. As I have been on trial for more than 13 months now, I am in a somewhat unique position to provide the perspective of a trial participant, or subject. This is, of course, not to be confused with medical advice which I am not qualified to give. What I can do though, is tell you about my own experience with this drug. Let’s pretend I am being interviewed:
How is the drug administered?
The drug is in capsule form. At this stage of the trial, 250mg twice a day is the standard dosage, as it was when I entered the trial. I take three gray capsules in the morning, and three more at night.
The first time you took the pills, what did it feel like?
I felt a little woozy; just a bit different or altered. I had severe diarrhea within an hour, as well as mild nausea. The diarrhea cleared up after several episodes that day, as well as administration of some immodium, and it was not an issue again. I felt somewhat fatigued as well.
Were there potentially more severe side effects as well?
My heart rate was monitored very closely initially, and at one point I had a questionable EKG (mild arrhythmia). It happened once and and proved to be a non issue. There was also the potential for liver inflammation, and my liver enzymes rose sharply after a few weeks. They never reached a dangerous level of concentration, and quickly began to decrease before settling at a slightly elevated level where they remain. It is interesting to note that when I had to take a holiday from the drug during surgery for my ankle, my enzymes dropped to a level that was very close to normal. Perhaps a week after the onset of regular dosing, I awoke with a very noticeable visual disturbance: it was as if everything had a light trail or ghost image. This effect was most noticeable in low light conditions, and/or when I was transitioning from dark to light. I would eventually learn that this is a condition called palinopsia and is a side effect of certain drugs.
What were the positive effects and how quickly did you notice them?
When I started the trial, I was coughing almost constantly and was noticeably short of breath. When I lay down at night my lungs “rattled” in a way that was all too familiar: I knew it was the cancer. I could tell that my immune system was depressed in general, as I had begun to have secondary infections and to feel crummy all the time. It was obvious to me that I was dying, and it was scary as hell.
The first dose of PF-02341066 was a lead-in dose. This meant that a whole week passed before I began daily dosing. Within days of taking the full dose, all of the above symptoms began to fade. It was truly amazing. By two weeks, I had no cough and I could breathe so much more freely.
Were there lingering negative side effects?
Nausea hasn’t been a big issue for me, but I do have days where I am queasy and on two occasions I have vomited. In the beginning, as a variation on the trial, we were not allowed to eat for several hours before and after taking the capsules, and the nausea was much more bothersome. Taking the drug on a full stomach definitely helps. For perhaps the first eight months, I would seem to hit a wall of fatigue at about 8 pm. I have noticed that exercising actually makes this fatigue far less noticeable, and I can stay up until 9 pm now–even stretching it to 10 some nights. I definitely require more sleep than I once did; perhaps averaging ten hours a night. After a few months, I became aware that the peripheral neuropathy in my feet and hands (a lingering result of chemotherapy) was more noticeable again. I am no longer so aware of it. The palinopsia, or visual disturbance is not so noticeable either, although driving at night is more challenging than it once was. I am unsure as to whether or not these side effects have actually lessened, or if my brain has simply adjusted to a new reality.
After several months of being on trial, I had a very sharp pain in my chest upon swallowing and I coughed up a small amount of blood. After questioning me about my symptoms, Dr. Shaw felt that it was esophageal in origin. A look down my throat with a scope confirmed the presence of an esophageal ulcer; likely as a result of an incompletely swallowed capsule. It was quickly resolved with several doses of Carafate. I now make sure to drink lots of water with my pills and I usually take a bite of something as well (such as applesauce) to make sure they all went down.
One interesting, if benign, side effect has been a sharply increased sense of smell. I can smell everything now with such acuity, that I feel kind of like a bloodhound. There are situations where this is not a good thing, but for the most part I enjoy this sharpened perception.
And how about lingering positive side effects?
Oh yeah. I feel great. Better than I have in years. I am strong, my immune system is in balance and perhaps more vigorous than it had been previously. I wake up every morning and sing a little song. It goes something like this: “I’m alive, I’m alive, I’m alive.”
What lifestyle changes has enrollment in this clinical trial entailed?
Well, obviously I commute to MGH in Boston with greater frequency. In the beginning, it was somewhat intense, but now I go once a month for PK’s (pharmacokinetics), a physical with Dr. Shaw and to pick up my drug supply. I have spiral CT scans every two months. I must obtain an ok for any new drug, prescription or over the counter, with the trial team before I take it. Because of my slightly elevated liver enzymes, I avoid hard alcohol for the most part (occasional teeny martinis and wee margaritas), but still drink red wine in moderation. It is necessary to record the time I take my drug each morning and evening as well as the time of the meal just prior. This is certainly the most tedious part, and I am not always good at remembering. Once or twice I have forgotten to take my dose of PF-02341066 as well. Luckily, it has a rather long half life, and I have simply waited until the next dose (per my doctor’s recommendations). And sadly, I can no longer eat grapefruit or drink grapefruit juice, as it interacts in a negative way with the drug. Ending on a truly positive note; my ability to travel, exercise, and go about my daily life has in no way been restricted. Although, when I broke my ankle Marguerite and Jose did tease me that there was a “no broken bones” clause in my clinical trial contract.
So is PF-02341066 really a miracle cure for cancer?
No. It is not a cure. Because I have a mutation of the EML4-ALK gene, my body would again manufacture cancerous cells if I were not taking an ALK inhibitor such as PF-02341066. This is referred to as onco-addiction: tumor cells are dependent on activated oncogenic signaling pathways, and the ALK inhibitor disrupts this process.
How long will it work for?
We are on a frontier here: so the correct answer is that no one knows for sure. EGFR inhibitors have been effective for some individuals for several years and in some cases, longer. However, it is not unlikely that eventually the cancer will “find a way around” these inhibitors. The fact that I have had stable scans for 13 plus months is a good sign, and I have a gut feeling that the cancer will be held at bay for some time.
So what then?
I can only hope that PF-02341066 will continue to be effective for a long time, and that other drugs that target ALK (and other mutations, for those who are ALK negative) are in the pipeline. In the meantime, I have been given the gift of more time, and each day is precious. I also have the satisfaction of knowing that my enrollment in a clinical trial has in some way contributed to the search for more effective treatments for lung cancer, and, perhaps eventually, for some a cure.
Thank you so much for all your carefully thought out information. I was diagnosed with Non-small cell lung cancer (BAC) Dec. 11, 2008. I received 6 rounds of Avastin/Alimta/Carboplatin once every three weeks. When that stopped working I took Tarceva for a few months. I do not believe that worked at all. I have now completed 5 rounds of taxotere. I see on the clinical trials site that I may have been eligible for a EML4-ALK mutation clinical trial if I had known I carried the mutation (I may have missed it because of the timing). Do you have any thoughts or information on getting the tissue testing done. I do not have any tissue left from the original Bronchoscopy. They did test for EGFR. Did you have a second Bronchoscopy or did they test for both mutations at the beginning? I do have a call in to MGH. Because of the new information they said it would be a week before they could call back. I’m thinking it is important to know for the future so as not to miss out on a trial. The lab with the four robots sounds amazing. It would be great to have the results for over 100 mutations on file for the future.
I live in NH also. It is uplifting to know you are close by, with the same cancer type, making your way to health.
Take care, Sherri
Sherri, As they are enrolling for phase III of the clinical trial now, if you have the ALK mutation, you may well still be eligible (there are certain requirements regarding previous treatments as well as a pre-trial physical and lab work). I was tested for EGFR four and 1/2 years ago, with biopsy material from my lobectomy. When I was tested for ALK more than a year ago, I don’t know if they used part of the original tumor sample (MGH stores them) or if it was a new sample from the biopsy I had prior to re-staging–that’s a distinction that I have always meant to clear up with my oncologist. Was your EGFR test negative? If it was positive, they would not test for ALK as they are mutually exclusive. If it was negative for EGFR and K-RAS (which is less frequently tested for and is also mutually exclusive to ALK) I believe there is approx. a 33% chance that you would test positive for ALK. It is now known that tarceva is ineffective for ALK mutants, and that was certainly the case for me.
I think you are right to assume that it is good to know whether or not you have certain mutations, as the treatment of lung cancer is certainly heading toward these targeted therapies. Best of luck to you, Linnea
I wanted to let you know I have an appointment with Dr. Alice Shaw next week. Both EGFR and K-RAS were negative so I’m quite hopeful that at some point, if I test positive for ALK, that I may at some point have success with the drug you are on.
Take care! Sherri
Sherri–that is great news! Keep me posted as to what happens and one of these days we should meet in Boston (or NH). Linnea
Linnea … I guess I’m not doing my job well enough if you have to “pretend” to be interviewed!
Great job helping all these folks out with some more information! You’re the best!
I guess Jon Stewart must have not been available…Linnea
OK: just a little funny. I feel privileged to have a voice and it is my pleasure to use it. Thanks for everything you do Katie.
I think you do a great job to provide this so upcoming and new information! It’s a prove of how loveable and caring you are and also how strong!
Caroline, thanks for saying that. I’m just happy that I am able to describe my experiences in a way that might be helpful to others. And I think you are so strong and inspirational to post about your own fight. You are in my heart and we are in this together. Love, Linnea
Linnea, Pfizer should definitely pay you for your work as a spokesperson. Thank you for your effort to make the information available to the public. You made me think that maybe I should do the same in Japanese as the information on this trial that’s available to the general public in Japanese is very limited. I even think doctors in Japan don’t know much about it, either.
Thank you for inspiring me, as always.
Yuki–I think that would be a fabulous idea. (Not the getting paid part, but that’s not bad either). As I said to you previously, you are so very articulate, so that would be a great thing for you to do. Hope you are well and getting excited about your trip home. Love, Linnea
Fantastic… really awesome issue. I will write about it also!
I read about your blog in the Team Inspire Chat Room. I am Stage IV adeno and just found out last week that I have the ALK mutation!!!!!!!!!!!!!!!!! I started a blog for my friends and loved ones to keep up with me (without my having to make call after call). If you don’t mind I’ll refer them to this one for the ALK explanation. I just told them to google it. I am readingbout your experience with interest and wish you nothing but good luck and good health.
Ellen, that’s great that you have discovered that you have the mutation. Best of luck to you too on this journey. Linnea
does anyone know if you can chew crizotnib pills. I have a tough time swallowing the tiny pills, let alone a capsule. I am ALK positive and start this drug in 2 weeks.