Friday, April 27, 2012

The Magic Stuff Called PCI 32765

Dave’s Great Adventure
Book 5, Chapter 2, Verse 1
April 26, 2012

“…there I was, under a sheet, naked except for some surgical scrubs they’d given me, but with the pants down around my knees….”

On Leap Day, 2012, February 29th, I was given the news that I had been accepted into the clinical trial of the new oral agent for combating chronic lymphocytic leukemia, the so-far unnamed drug that goes by the clumsy label of PCI 32765, the manufacturer’s in-house development code, I presume. I instantly assumed we’d be starting the study right away because just a couple of days before, during the fifteen minutes between being told I was in the study and being then told that I was excluded, Dr. Keating’s staff had been frantically trying to arrange the things I would need before I could begin taking the new drug, such as a bone marrow biopsy, an infusion of Rituxan and more. I was thinking we’d have to go back to the hotel to extend our stay.

But, almost as soon as I was told that I was in the study, I was told that we’d start the protocol, oh, maybe in the middle of April. What! It appeared that when I had briefly been excluded from the new study two days previously, I’d lost my place in line, as it were. I asked if we couldn’t start any sooner, as I was extremely anxious to get started for many reasons. Gracy looked at her schedule and said it was filling rapidly but maybe we could start on March 27th, four weeks away. I asked if she would book me into that slot as it sounded a bit better than sometime in April, which sounded years away to me.

We left Houston with that date in mind, and were very thankful to be in the study, but I was apprehensive about waiting four weeks to start. The new drug was just about the only thing standing between me and a bone marrow/stem cell transplant, with all its possible risks and complications, including, at a minimum, a 5-10% risk of dying, according to Dr. Khouri. I was fearful that something would happen to again get me excluded from the study; I’d get sick with pneumonia, I’d be injured in a car wreck, I’d fall and break a hip, I’d have a heart attack, or any of the myriad things that can normally happen to a 65 year old guy. I really wanted to get the study started and I wanted to make sure that I stayed healthy during the intervening four weeks. But I didn’t want to become a recluse.

Months before, probably last Fall, we had planned a trip to Moab, Utah, to be with the Leukemia and Lymphoma Society’s Team In Training (TNT) for a half marathon that is run there every March. A group of TNTers from Colorado, including some good friends, was going to be running in the event and I’d been invited to speak at the dinner which is held the night before the event. Generally a survivor of lymphoma or leukemia speaks to the runners, who by then have spent months training for the event and raising money for research and patient assistance. We survivors want to let them know how much what they’ve done means to us. But for many months I hadn’t been sure if I could keep this commitment, as I’d been undergoing treatments with the Arzerra all Fall and then found that my lymph nodes were swelling massively in February. But, when we found that I wouldn’t start the new therapy until late March, it appeared that I would be free to attend.

I had some reservations. Generally Kathy and I try to avoid crowds and folks who are obviously sick with coughs and colds, and we’re obsessive about hand cleaning, avoiding shaking hands, touching doorknobs and such. Going to the event would mean doing precisely what we usually try to avoid. We’d be traveling on crowded airliners, sitting in airports and sitting near lots of strangers in shuttles. At the marathon event I’d be among crowds of people, shaking lots of hands and hugging lots of folks. But, I really wanted to do it. I’ve been a part of TNT for five years now and they are just routinely wonderful people. I wanted to be with them and to be able to tell them my story. So we went. Everything went well and we had a great time with our teammates in Moab. And I didn’t catch a cold, either.

But during that month wait, I could feel the masses in my neck and under my arms getting bigger every week, and my belly was getting more and more distended as the previously discovered tumors kept growing. Only later was I to find out how much they had grown. All I knew was that it was getting harder to breathe and that I couldn’t eat very much. There just wasn’t room in my stomach and chest. And the “marbles” in my armpits grew into “golf balls.”

Before and after our trip to Moab, Kathy and I were planning out our next month. We knew the study would include many weekly trips to Houston, at least initially. That wouldn’t leave a lot of time for domestic tasks, so were setting up lawn care, paying bills and asking our neighbors to get our mail and papers and such. And then we left for Houston, to start the new drug regimen.

But there were still a few hoops I had to jump through. Our first day there, on the previously appointed March 27th, I had labs and tests scheduled virtually all day, from early morning until my last appointment, a CT scan, scheduled from 7PM to 10PM. That was to prove to be the most entertaining of my evaluations. But I’ll get back to that.

I had multiple tubes of blood drawn first, before seeing Dr. Keating and his nurse Jackie. They did a physical exam on me and noted the sizes of my palpable masses. The tumors under my arms were now about golf ball sized and the ones in my neck had grown to about marble sized. Then I had an EKG scheduled, to ensure that I had no significant heart irregularities (besides my long-standing irregular heart beat and my floppy mitral valve). I was able to get my EKG done very early, in the morning rather than the 3PM it had been scheduled, so we thought that perhaps we could get my bone marrow biopsy, scheduled for 4:30PM, done early as well if we checked in early. We were hoping to get a bit of a rest in the afternoon before we went for the CT scan at 7PM, since it promised to last until late. And since I was instructed not to eat anything for three hours before the CT, we wanted to have a break between the bone marrow biopsy and dinner time so I could eat before the three hour limitation started.

We checked into the bone marrow biopsy clinic at 1PM. I told the receptionist that I was very early, but hoped that I might be able to get in before the scheduled time. She let on that, yes, there was in fact a good chance I’d get in early. So Kathy and I found a seat, away from most of the other patients, like we always do, and we waited. And we waited. And we waited. 2PM came, 3PM came, 4PM came and went and I hadn’t been called back. So much for getting in early. We killed the time with our smart phones, playing “Words With Friends” and “Draw Something” with our kids, long-distance. I think they were supposed to be working, but instead, they were entertaining us. But it really did help to pass the time. Finally, I was called back at 4:30.

Now, a bone marrow biopsy is probably one of the most feared tests a person can be told they need. I’ve seen folks weeping almost hysterically in the biopsy waiting area, so frightened are they. People like to tell others about just how excruciatingly painful it is. And, in fact, a bone marrow biopsy can be painful, but it doesn’t have to be. I’ll tell you that if any of you out there ever have to have a bone marrow biopsy, go to Houston and get it done at M. D. Anderson. Some places it’s so painful they give powerful IV drugs to help block the pain, but at MDA, you’re wide awake and totally conscious. There, they operate much like your dentist does. They use lots of local anesthetic and they wait a while to make sure it’s working before they bore into your hip bone to drill for marrow. The process, though not completely painless, is probably less painful that your average flu shot or falling down and spraining your ankle. And, the biopsies are done not by doctors either, but by trained nurses and PAs who do dozens of them every day. And they’re very good at what they do.

So, I ultimately finished with the biopsy but by then it was 5:30. We now had only thirty minutes to find a place to find dinner before I was forbidden to eat, in preparation for the CT scan. We quickly headed towards the Mays Building which is at least a quarter of a mile away, where the CT scan was to be done. It’s so far away that they have a golf cart shuttle system to take patients and staff to and from M. D. Anderson’s main building to the Mays Building via sky bridges. We had been there before and knew they had several snack bars so we headed for one. But, on arriving there we found that the building looked almost completely shut down for the night and all the snack bars had closed. So we backtracked a few hundred yards to the Rotary House International Hotel, which is also attached to MDA by sky bridges. We knew they had restaurants which operated during the evening hours and we were able to get in there and get me fed before my 6PM cutoff time for eating.

After hurriedly finishing off my nutritious meal of fish and chips before 6 PM, we started walking back the couple hundred yards to the Mays Building. As we had noted, the whole building seemed to be pretty much shut down for the night. Most lights were turned down, desks were empty of receptionists and very few folks were anywhere to be seen except for an occasional security guard making his rounds. I allowed myself to think that with so few folks around we might actually get into the CT clinic early and be done before the appointed 9-10PM.

So you can imagine our surprise when we got up to the 7th floor CT clinic and walked into what looked like the midway at the carnival. It was brightly lit with perhaps 75 people milling about in the waiting area, sleeping on chairs, covered with blankets, reading, listening to their Ipods, and so on. A scrolling informational sign conveyed bad news: “One Unit Down For Maintenance, Expect Delays,” it said. Just like you see along the highway during construction.

I checked in for what was to be a long wait. I knew I had to “prep” for the scan, but previously that meant only drinking about a quart or so of salty-sweet “contrast” and then waiting about ninety minutes. But this prep was to be a bit more complicated. First I was instructed to drink about a pint and a half of a thick, viscous barium “fruit smoothie” within about fifteen minutes. Very chalky, and I got it down as fast as I could. It was tolerable. Then, a half hour later they called me back to put an IV in my arm. I was to have some IV contrast injected during the test as well. And, they told me, I was to have some “rectal contrast” too. “Uh, what?” “Yes, you’re getting rectal contrast too. Sign here to acknowledge that you’ve been told.” I signed as instructed.

Then we waited and waited. Folks were going back from time to time but the place wasn’t clearing out very fast. Finally, at about 10PM I was called back to the exam rooms. I was told to undress completely, underwear, socks, everything, and put on some hospital scrubs. Then I was given yet another bottle of “fruit smoothie” to drink and about 30 minutes later was taken into the CT room. They placed me on the table and covered me with a sheet. The nurse said, “Pull your pants down and turn on your left side.” I knew what was coming, and with that, yikes, she inserted a nozzle into my nether aperture!

So, there I was, under a sheet, IV in my left arm, my belly heavy with barium "smoothies," and naked except for the surgical scrubs they’d given me, but with the pants down around my knees and a tube stuck up my butt. I smiled, a wry smile. “This,” I thought, “is probably like what I put my patients though for so many years.”

The CT went quickly after all the waiting and we were glad to get out of there. But by now it was 11PM and the building really was shut down. We had to have security let us out and direct us to a shuttle to take us to the parking garage, about a half mile away, so we could get back to our hotel.

But, I had finally jumped through all the hoops, I could start the study. The next day I had my first dose of Rituxan which I had to have in me before starting the PCI 32765. I had a bit of a reaction to the anti-CLL antibody drug, as it was blowing up billions of CLL cells all at the same time so I needed some steroids, antihistamines and some Demerol to stop the shaking chills I was having. But, other than that it went well.

The PCI 32765
Astounding…just astounding.
The day after the Rituxan infusion I saw Dr. Keating and Jackie one more time. Things were looking great, though I did find that the CT scan showed that the largest tumor in my belly, which had been 8 cms.(about the size of an orange) in February, was now 16x8 cms. in size, about the size of a squashed cantaloupe, so fast was it growing. They cleared me to start the PCI 32765!

I had been given bottles of the drug a couple of days before and had immediately broken open the seal on the bottle to see what this new wonder drug looked like. It was just a bunch of generic, grey capsules without any markings on them whatsoever. But now I was cleared to take it. I had supposed that since I was taking an experimental new drug for the first time they would want me to take the first dose while I was with them so they could watch me for a bit to see how I handled it, but they didn’t want me to stay at all. Instead, they said “Bye bye” and with that we were off, driving back to Denton. The instructions with the drug said I couldn’t take it until at least two hours after I’d eaten, and since I’d eaten breakfast, I couldn’t take the drug while we were in Houston. Instead, I ended up taking my first dose while driving up Interstate 45 at a speed somewhat faster than the posted 75 mph limit. It was a good omen.

I’ve now been on the PCI 32765 for four weeks, and it has worked astoundingly well and with astounding rapidity. I could feel a difference in my lymph nodes under my arms within days. Within ten days my belly was not so distended. And now, after four weeks on the stuff there are no longer any palpable masses in my armpits, neck or belly. I feel so absolutely fortunate to have been selected to be one of the 40 high-risk patients in this study. The results are unbelievable so far. Now, it’s only been a month so far, but other folks in the previous Phase I study have now been on the drug for up to 18 months or more and still no significant problems have developed. I expect more good things. I’ll “get” to have another CT scan in a couple of months to see how the 16 cm. mass in my belly is doing, but already I can tell from the fact that my abdomen is flat now, that it’s shrinking rapidly.

And that is enough for now. I have let this message get far too long so I’ll close and send more technical details of the drug, and answer your questions in another letter.

If you’ve actually read all this, I thank you for your patience with me.


“We also know that everyone gets their own box of challenges, they just come in different size boxes with different colored bows. We hope your box has been lost in the mail.”—from our friend Sarah, whose husband Mike is battling an incurable Stage 4 lung cancer. They’re going on a cruise to England and Scotland this summer.

“I’d rather die living than die dying.”—Steve Appleton, chief executive of Micron Technology (semiconductors) who recently died when his high-performance airplane crashed in Boise. (Mike and I agree with this philosophy.)