Monthly Archives: February 2012

Just desserts

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!

Calculating risk

Thursday I traversed the frozen surface of the pond for perhaps the last time this season. The ice is thinning quickly. I had on my rubber boots and stayed what I felt to be a safe distance from shore: should I break through, the water would not be over my head. I got some fantastic photos and considered the little adventure a success. However, over dinner that evening when I mentioned that I’d been on the pond earlier, David and Peter were furious. Peter wouldn’t calm down until I promised I wouldn’t go out again.

I have always considered fear the enemy; something to conquer and overcome and I’ve had a lot of practice. Being risk adverse and scrappy has been an asset now that I have lung cancer.  As a participant in a phase I clinical trial, there is the potential for unforeseen and possibly life threatening side effects of treatment itself. Before you are given your first dose of an experimental drug, you must read through and sign consent forms which acknowledge this risk. It is something most healthy persons would never do. When you have a terminal illness, it is similar to coming to the edge of a ravine with a tiger on your trail. Between you and safety is a rickety bridge that may or may not support your weight. However, even chancy passage is an easy decision when the alternative is certain death.

Last week, the first night in the hospital, I pumped Dr. Shaw for information regarding the worst case scenario. She hesitated, but I assured her that knowing helped me feel more in control. When David had to leave for home, I told him goodbye and that I loved him and that if anything happened, I was so sorry (I figured that covered pretty much everything).

That night, when I finally fell asleep, I  dreamt I was kneeling in a field next to a man who seemed to sparkle with light, as if he were made of fireflies. And then I recognized the sparkling figure; it was my Grandpa Roy. It’s been almost thirty five years since my grandfather passed, and I was shaken the following morning. It was almost as if I’d paid a visit to the narrow place between life and death.

It was merely a dream. My enzyme values continue to fall. Slowly. It is a time for patience, and that is a virtue I cannot claim.

A bit too close to the edge

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.

Parting Shot

Change of Scenery

Thanks so much to everyone who left comments on the previous post. As you can see from the photo, my little bump in the road got a bit bigger and I am writing this from a hospital bed.

Shortly after I published the previous post, I got a phone call from Dr. Shaw with the results from the local lab. My liver enzymes, rather than going down, had now risen to more than four times their level on Monday. Essentially, my liver was being poisoned. There isn’t an antidote for hepatotoxicity, but Alice (Dr. Shaw) wanted me to come in for monitoring. Significantly elevated liver enzymes (ALT/SGPT and AST/SGOT) are a sign that rapid cell death or injury to the liver has occurred (as the cells die they lyse, or break apart, and release enzymes into the blood stream). However, even a severely injured liver can maintain function. My circulating levels of bilirubin and alkaline phosphatase were both within normal limits, which was reassuring. In the case of actual liver malfunction, they would be elevated as well. However, should the ALT/AST continue to rise, function could be affected as well.

So, off to the hospital I went. Initially I was assigned to a double in an acute care wing. Dr. Shaw checked in and then it was time for some tests. Around 10 pm my liver enzymes were tested once again and they were slightly lower than the one that morning but still quite high. I had a chest x-ray as I was still coughing (and the levaquin was now being held as well) but it came back clear for pneumonia. I was poked and prodded and asked if it hurt until it finally did. I was given an ultrasound of my abdomen, which showed no lesions (thank goodness for that). And, just to rule out anything else that could have instigated the elevation, I was tested for everything under the sun that could affect liver enzymes. Hepatitis, HIV, Epstein-Barr, drugs and alcohol (just in case the patient wasn’t disclosing!).

My roommate was a lovely woman, but anything other than a private room in the hospital is just really hard. Two people, both sick but generally not in the same way, a shared bathroom and a very modest space full of apparatus that is often beeping loudly, a parade of doctors, nurses and visitors as well as the inability to not hear everything that is being said and happening on the other side of the curtain which divided us. It is really not conducive to sleep or healing.

Fortunately, by late Friday, a room had opened in the Lunder building. It is a new wing of Massuchetts General Hospital which is devoted to cancer patients. It is located directly adjacent to the Yawkey center, where I receive my outpatient care. All the rooms are private, spare and modern  and graced with large windows as well as pull out couches for visitors. It’s really nice.

So, that’s where I’ve been hanging out. Aside from a twelve hour period of diarrhea (unrelated to the liver, so more tests) I have felt under the weather, but not too bad. Each day my enzymes have been a bit lower; at first the change was incremental, but the downward pace is increasing. My appetite is coming back as well, and I’m starting to feel restless (a good sign).

It’s now Sunday. Half an hour ago I was handed my discharge papers. My ALT is still in the triple digits, but at this rate, I should be back to normal soon. Once home, I will resume the levaquin (now felt safe to reintroduce) as my chest infection has lingered. On Tuesday I’ll be back in Boston for more labs, a chest CT scan and a quick meeting with Alice. The big question will be, where do we go from here?

One two punch: medical and emotional update

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.

Heart y’all

I’m feeling nostalgic for those February fourteenths where my kids were still small. They’d arrive home from school sticky with pink frosting, a paper bag stuffed with valentines from their friends in one hand, a homemade card for their Mom in the other. One of my favorites: