Gleevec: Explanation

I was talking with a friend about my previous entry about Gleevec, and found she’d come away with some confusion, an unintended interpretation. I’ll try to put my own understanding into better perspective and explain a bit more clearly.

Results of initial Gleevec testing with CML (Chronic Myeloid Leukemia) came as a surprise to researchers. Ten years ago they were only looking to verify its safety to test on people rather than its effectiveness; they weren’t expecting to find such high response rates in such early trials. But what they saw drove them to look at the patients more closely to see what was common about them. That’s when they discovered the “Philadelphia chromosome”, named for the lab where it was discovered. This chromosome malformation they had discovered led them to identify the first protein identified as a cancer-causing agent.

When they looked around at other cancers, they found similar reactions and high occurrence of the defective chromosome with GIST (Gastrointestinal Stromal Tumors). Soon after that, the FDA approved Gleevec for use with CML and GIST, making the drug commercially available.

In the meantime, other researchers in other types of cancers jumped on the bandwagon. Maybe they’d find a similar genetic mutation and the high response rates in their disciplines as well. Some of those other researchers, of course, dealt with melanoma.

There are experimental trials currently underway with melanoma to prove the concept. In order to get into such a trial, the drug company requires a four-week genetic workup to identify presence of the deformity. But the doctors on the battlefront have their own anecdotal evidence to identify who is most likely to be receptive to Gleevec treatment. My doctor and her geographically far-flung colleagues have independently observed that melanoma patients whose primary lesions start in two different ways tend to be the best candidates, while other, more “traditional” forms of skin lesions don’t usually respond. The responsive cancers start in moist places of the anatomy, or on the palms of hands and on the feet.

My doctor added her own 2-plus-2 and realized that I’d be an excellent candidate for Gleevec. She didn’t want us to wait four weeks for the drug company to come up their own verdict about me when her own intuition told her to go ahead. We were able to start me on the drug right away because it is commercially available.

Jewish penicillin

Generations of Jewish mothers have believed that chicken soup has restorative powers. And if it doesn’t, so can it kill you?

My latest doses of the remedy have come by way of my ex. Last week he brought me a quart of wonton soup, a modern day, Chinese-American variation, and he laughed when he saw the way I guzzled and relished the delicious broth.

This evening he called as I was out picking up a prescription and informed me he’d just made a big pot of his own delicious version. Would I want to stop by for some on my way home?

I did. And it was truly wonderful. I had dinner of salad and chicken soup with him and his girlfriend. They treated me royally.

I need to say a few words about my ex.

Divorce isn’t easy… no kidding. I’ve never regretted ours, though it hasn’t always been easy in the last ten years since, or especially in the years leading up to it. But it gave both of us our lives back and allowed us to become better friends.

The past several months I’ve had some very serious problems to deal with and he has been a tremendous help to me. I had to come to grips with some of my own demons in order to ask for and fully get his attention, but once I did, he was there.

Most recently, he has been extremely concerned about my health, and helpful beyond anything I would have expected at less stressful times when it's easier to keep at arms length. He picks things up for me, brings me food, drives me places, and sits and keeps me company when he sees I’m ailing. He’s observant and smart, and knows firsthand what kind of distress I’ve been in, and he’s reacted empathetically. In short, he’s been terrific.

This should come as relief to some of you who have heard anecdotes about some of our less pleasant interactions. His behavior can leave people scratching their heads, but I’ve always believed in his basic decency (well, almost always). The past months, and the chicken soup, have brought that home to me very clearly!

Catch-up: More pain and tiredness at home

Thursday morning I was still high from my infusion of steroid the day before. My back pain was greatly reduced, but I was very anemic, causing a push-me-pull-you kind of effect. I’d bend and reach and stand and everything seemed okay. Then I’d take half a dozen steps and collapse, winded, against a wall.

I was already scheduled for a blood transfusion this morning to address the anemia. I didn’t sleep well last night, or nearly long enough, so by the time I arrived at the Cancer Center, I was in such agony that we had to deal with the pain first before getting on with the transfusion.

Another cocktail of intravenous drugs: steroid, Dilaudid (said to be a Lenny Bruce favorite), anti-nausea, hydrating fluids, followed finally by two units of blood. I was in the Center all day, drifting and dozing and accepting the mix of fluids into my body.

Now that I’m home, I’m very much needing to sleep, but wanted to get some information up here first that I know some friends have been waiting to hear.

There will be more tomorrow….

Catch-up: Off chemotherapy

“You’re not getting chemo today.”

For a variety of reasons, my doctor pulled the plug on this latest course of chemotherapy treatment. Wednesday’s blood labs showed low platelets again, which alone would have postponed this round of treatment, but in short, I haven’t tolerated it well at all, and it’s not working.

But that wasn’t the whole reason. My doctor was grinning.

“I was hit with divine inspiration. There’s a new drug. It’s experimental for melanoma and I can get you into the next round of study, but there’s a four week wait while they work up a genetic profile to see if you meet the criteria. I don’t want us to wait and we don’t have to. The drug has been approved for other forms of cancer, so it’s available commercially. I just wanted to talk to you about it first so I can have it overnighted to your house and you can start taking it tomorrow. I guarantee, by the time they can get the study done, we’ll know by your response if you fit the profile.”

She then proceeded to tell me about Gleevec.

Gleevec is not chemotherapy. It’s not toxic, has minimal side effects; it doesn’t cause you to lose your hair. It’s a drug that takes a different approach. Instead of targeting cancer cells and everything else in its path, it goes after specific proteins exhibiting a particular genetic mutation. A high correlation of response was initially noticed in patients with Chronic Myeloid Leukemia (CML) and certain gastrointestinal tumors (GIST), which tend to exhibit these defective proteins, the first case of proteins known to cause cancer.

Now here’s the kicker: studies are underway to find other cancers that exhibit the same type of genetic abnormality. In the case of most melanomas, Gleevec has no effect. But various independent studies have shown that there are a couple of forms of melanoma that start in “non-standard” areas, which do tend to have the defect. The first type is in moist areas of the anatomy, such as sinuses, mucosa, and vagina. The second type is when the primary lesion is on the palms of the hand and on the feet. If you remember, my initial lesion in 2002 was on the side of my heel!

My doctor’s excitement about this new drug is contagious. I took my first pill last night. There’s so much more to write about it, but I need to get some sleep tonight. Look for new posts tomorrow.

Catch-up: Doctor visit on 12/10

So much has happened in the past couple of days, it feels like a week has passed since my last post, so I’ll probably have to break this up into multiple entries.

I was due to see my doctor on Wednesday for treatment and to discuss scan results. When she walked into the examination room, I was curled up on the table, asleep.

“This isn’t you,” she said, shaking her head.

“I’m exhausted all the time,” I explained. “and in pain.”

I told her about my experience with Advil the previous afternoon, how two little blue gel pills had done more to address my pain than the morphine I’d been taking for a week before.

“It’s obvious the pain is inflammatory. We can fix this.”

She had already included the usual dose of Decadron in my premeds, and she prescribed the same steroid for me to take in pill form at home on a daily basis. Steroids are longer acting and don't interfere with clotting, as ibuprofen can. When we begin to see reduced inflammation from the steroid, we can also start tapering back the Fentanyl patch dosage, since it's not a good idea to alter too many variables at once.

Also, Fentanyl is a strong, addictive, narcotic, and we’ve all read stories and seen movies about “cold turkey.”

So for now, we just add daily steroid.

Drugs

The last few days have been more misery for me.

When I reported how much pain I was in, the doctor recommended I replace my anti-inflammatories with yet more narcotics. She gave me a prescription for a drug called MSIR; that’s Morphine Sulfate Immediate Release. I’ve been taking MSIR for about a week, and the pain didn’t seem any less. The more I took, the groggier I got, so I limited myself to one pill a day. Walking became more of a chore. I was exhausted, achy, and less and less able to function. But at least on one pill a day I was able to stay awake for six to eight hours at a stretch.

I was scared.

This evening, before my first nap of the day, I took two Advil. When I woke an hour later, my pain was greatly diminished and my head a whole lot clearer! What a relief to make this discovery. I knew I was reacting badly to the morphine, but I didn’t realize the extent to which it was robbing me of my vitality.

In a conversation with my ex earlier today he recommended that I not drive. He was concerned that my reflexes and reaction times were slow and that I was a danger to myself and others. Although upsetting, I had to agree with him. He offered to drive me to the train station for my doctor’s appointment in the morning and I sadly agreed to the arrangement. Post-nap, I now feel that my head is clear enough that by morning I’ll be able to drive myself!

I will, of course, discuss all this with my doctor. And I plan to stay away from morphine!

Aftermath

By the time I got to Grand Central yesterday afternoon after leaving the client, I was Cinderella and my gown was starting to shred. By the time I got home I could barely walk again.

Per doctor’s orders, I increased the dose of my pain patch and got into bed at 7:30. I didn't take an anti-inflammatory before falling asleep, hoping the patch would do it by itself, but I woke during the night in a great deal of pain, so I took a Naproxen then. I was in pain a lot of the night, but managed to sleep until 10:30am when I woke up groggy and still in some pain after more than fourteen hours sleep!

My doctor says I probably overdid it.

The doctor’s admin just called to let me know she’d gotten the next scan approved and scheduled for tomorrow afternoon. She’s the greatest at getting things done!

So it’s been another lost day: naps, pain, lack of focus. I hope we can get to the bottom of this soon.