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.

The little buggers are on the run!

I had my second PET scan on Monday, a follow-up diagnostic test just like the one I had in mid-June. This one was administered to measure the effects of my first six weeks of chemotherapy.

The procedure started with an intravenous infusion of radioactive glucose and a large drink of barium sulfate. Then I sat for about an hour while my body took up the fluids.

Next step was a CT scan. I lay on my back on a table that slides into a huge, space-age looking device. If you’ve never encountered such a machine, in person or on the likes of Grey’s Anatomy, this very imposing piece of equipment is a large, round, open-ended tunnel that projects x-rays toward you as you slide slowly through it. Unlike a simple x-ray machine, it records a series of images that present a three-dimensional view of the subject’s insides. It’s not painful or particularly uncomfortable. You simply lie still as the table slides to the proper positions to photograph what the doctor wants to see. This procedure took another hour, as they scanned my entire body, head to toe. A trained radiologist later reviewed the recorded images.

All cells consume glucose, but malignant cells are particularly greedy. They have a higher rate of metabolism than normal cells, so gobble up the glucose voraciously, and in the process, they light up from the radioactive substance. The radiologist looks for these metabolic “hot spots” to determine where tumors are growing.

In June, they identified about ten tiny nodules. This wasn’t a lot of cancer, either in size or amount. The largest tumor was less than two centimeters. Two months later, this past Monday, there were no hot spots at all! All the glucose was taken up equally. There were no visible pinpoints of light in the PET portion of the scan.

So where did they go? Well, the tumors are still there. They are dead and dying, but my body hasn’t fully absorbed or flushed them. They show up on the CT images as dull concentrations of cells, but there is nothing “hot” to be found.

I met with my oncologist this morning. She is very excited about these results. Needless to say, I am also. She tells me that when patients respond to this treatment in this manner, they respond “completely.” They go into remission “forever.”

Those are actually hard words to hear. I’ve been so very anxious the past few weeks, increasingly so as the date for the PET scan approached. I’ve been preparing myself for the best possible outcome, but I also have experience being blindsided. Twice, cancer fell out of the sky and took over my life. Twice, I got phone calls informing me I had melanoma I had no suspicion was there. At the same time I felt that my body was strong and healing, I was afraid to ignore the possibility of unwanted results.

“And how long is forever?” I asked, cautiously optimistic. After all, I was cancer-free for five years until this spring.

“Eight years,” the extent of the research so far with this clinical trial. Patients continue to get scanned once a year, but so far, their cancer hasn’t returned.

Where to next?

This coming Monday I’ll start the second treatment cycle. Another six weeks of drugs, starting with a weeklong infusion of Genasense. Genasense is the experimental drug that acts as a sensitizing agent. It alters the melanoma’s DNA so it’s no longer programmed to live and grow forever. In its weakened state, the melanoma is very susceptible to the killing power of the Abraxane infusion that ends the first week.

I will undergo at least two more entire treatment cycles and possibly a third; that’s another four to six months of managing side effects and missing my hair. On the positive side, the treatment is moving in the right direction, and I feel about a hundred pounds lighter!

What day is it anyway?

I just had the most disorienting experience!

I was feverish much of the day, starting around 11 AM. Fever spikes can occur any time during the seven days of Genasense infusion, and mine went from 101.3, when I first noticed it, to 102.9 a half hour later. I graduated from Tylenol to Advil to get it under control, and it hovered around 100° for the rest of the day.

At 5 PM, wiped out from fever in combination with the heat and humidity of the day, I took some more Advil and lay down in my clothes for a nap. Next thing I knew it was 7 o’clock.

I had slept fourteen hours, and I had missed my nightly Temodar chemotherapy pill!

I put in an off-hours call to my doctor and raced around getting ready for my 9 AM office appointment to draw blood. My doctor, and the nurse who monitors my participation in the program, are both out of town at a conference, so I called and spoke with a covering doctor who isn’t as familiar with the protocol for this trial. He looked into it and determined I should wait until tonight for the next dose. Three days into the program and already I’d flaked out!

I babbled on about sleeping fourteen hours and told him I’d be in the office later today for labs.

“You mean tomorrow,” he said.

“No, today, Thursday,” I said.

“Today’s Wednesday.”

I stared at my “Drug Diary”, still thinking it was morning, and simply could not figure out how I’d stuffed all those hours into the wrong day. I’d written notes about what side effects I had and what drugs I took, but had I made Wednesday up?

Finally I looked out the window and noticed the sun was going down, not up.

Phew... I didn’t miss my dose after all.

First day of chemo

I was pretty bummed this morning anticipating my first day of chemotherapy. But the physical effects so far are minimal and for now, it's mostly a matter of getting to know the details and working it into a routine. The doctor said I might have fever tonight, so I've been taking Tylenol proactively every six hours, and so far, nothing.

The complete treatment cycle takes eight weeks; six weeks of drugs followed by two weeks of rest. During the two weeks off, I’ll have another total-body PET scan. I’m not sure what they’ll be looking for to determine whether to continue or not, but based on their measurements, we’ll repeat the treatment cycle up to a total of four times.

The six weeks of drugs is actually two three-week mini-cycles. I started today with the experimental drug, Genasense. A nurse inserted a special needle through my skin and into the cap of the mediport. A long tube runs from the needle through an electronic pump, into an IV bag. The pump is a 4x5 inch brick that sits with the medicine bag in a fanny pack that I wear around my waist or as a shoulder purse. The pump constantly monitors and times and dispenses the proper amount of drug. I don’t feel it flowing or anything, but every once in a while I hear a low sound, like a camera lens going into focus.

I’ll be hooked up to this pump for seven days. Next Monday, when the IV bag empties, I’ll be back in the doctor’s office to remove it, and to get an infusion of another drug, Abraxane. That’s it for IV drugs until the fourth week, when I start back on the Genasense pump. During the entire six weeks of drugs, I’ll take one Temodar capsule per day.

Those are the treatment details. Boring as they may be, with names that are hard to remember, it’s comforting for me to have it spelled out into a plan of action. It’s a pattern and a rhythm I can follow. My visits to the doctor’s office will become routine.

There’s a special floor for the IV treatments where I sit in a private “room”. They call it a room, but it’s only three walls and a curtain. Still, it’s private enough, with a reclining chair, a phone, and a TV that I didn’t watch. I brought my computer and hacked into their network to get my email. It was actually kind of a relaxing day, apart from all the needle sticks.

Now I have to figure out how to share my life with this package of medical electronics I’m carrying around for the next week. "Get creative," the nurse said.

The tube is long enough to leave the pack outside the shower while I'm inside, and I can thread the tube under my clothes pretty successfully. But it's going to make sleeping a little tricky. I'm mainly afraid I'm going to somehow tangle in it and pull the needle out! And there's the issue of what to do if or when I start beeping, which can happen if the tube gets kinked. So far it hasn't happened, but I imagine it can be embarrassing. You know, like a cell phone going off in a quiet lecture hall.

Really good news

It’s Monday night and I’m breathing a huge sigh of relief. I’ve got a course of action, a positive direction. My life holds promise again!

My 2 o’clock appointment with the oncologist stretched out to nearly 6pm. Followed by a celebratory dinner with my sister.

First came results of yesterday’s PET scan indicating confinement of malignant cells to my lungs. There are about ten tiny bilateral nodules, consistent with the findings of last month’s pulmonary biopsy. Surgery is not an option in this case. The target is too small and too scattered. Apart from the invasive nature of surgery, there’d be no guarantee of getting them all, or that more wouldn’t replace them.

What options are there then? There’s chemotherapy. The rate of improvement for a course of standard chemo may not be much to write home about. But we can aim higher. My doctor runs clinical trials that mix chemo with experimental drugs that act as a kind of booster, where experimental means a drug not yet approved by the FDA.

The trial she recommends combines two traditional anti-cancer drugs (Temodar and Abraxane) with Genasense, an experimental one with exciting possibilities. It has already achieved eleven of the twelve FDA requirements and it has my doctor’s team lobbying for its acceptance. She’s been invited to Spain in a few months to present her findings in conference there.

So I’ve signed up to start this trial next week. My doctor’s enthusiasm is contagious. Her findings so far indicate that patients who respond to this treatment respond “completely”. She’s achieved a high rate of total remission where other treatments had limited success. Even more striking than overall statistics is the success rate achieved in patients with normal levels of blood enzyme LDH. She’s excited about the potential in my case where I am healthy and have excellent blood numbers. There are potential side effects, but for the most part patients are not sickened as they typically are with chemo.

I’m sure I’ll have plenty of mood swings over the course of the next many months. This course of treatment runs in eight week segments: six weeks on medication and two weeks off during which they run more CT scans. It can be repeated up to a total of four cycles. Most of the treatment is administered at home via pills and by pumping the experimental drug through an IV device embedded under my skin near the collarbone.

Right now I’m studying the materials my doctor has given me, anticipating placement of the “mediport” IV device on Friday, preparing for the eventuality of losing my hair, and thinking about the client work I need to get done now that I have some of my mind back.

More updates to come….