I was obviously reaching for anything, and taking it seriously. In my notes, I see a confirmation number for MD Anderson—051102162016FIK—and a registration for an appointment for a scan in the hospital in Houston. There were the names of the nurse-practitioners all across the country—the only people who actually take the time to talk with us about our options: Ann. Blanca. Julie. Jacqueline. Noel.
There were so many things to think about it made our heads hurt. The point of a clinical trial is to test—in people—how different drugs work. The trials aren’t designed for patients. They’re designed for science. Each design differs depending on the type of drug and the knowledge that the researcher is seeking. Some are logistically difficult. One—in a faraway state—required daily injections in a hospital for thirty days. We would have had to move there for at least a month. What about the children? Unless we thought this was a sure bet, that one seemed out. Some of them were testing a new drug against nothing at all. We didn’t want to do that. After all, if there was a chance that half of the participants were going to—without knowing it—get only a placebo, then that meant our already slim chances would be cut in half. Some of the studies were testing new drugs against the existing standard of care. One of these compared a new drug combination with interleukin-2. That meant there was a 50–50 chance Terence would wind up with another round of the IL-2 that made him so miserable in Lexington. No way we were going back to that.
Some of the trials—a lot of them, in fact—specifically excluded the odd cancers like papillary and collecting duct. Once we read deeply into the rules of some intriguing trials, we realized that the researchers were limiting their subjects to those 80 percent who had the common clear cell variety. Some of the trials—like ones for a vegan diet or for laetrile—appeared to be designed simply to rule out treatments that patients demand but that doctors didn’t think hold promise. And some, I learn much later, after Terence’s death, were known informally and privately as “throw the spaghetti against the wall” trials. During these years, a dawning recognition that the place of origin of a cancer—bladder, kidney, breast, colon—might be less important than the cancer’s genetic composition led researchers on flights of possibilities. If a drug worked against colon cancer, let’s try it for breast cancer. If it worked for breast cancer, let’s try it for kidney cancer. That, weirdly enough, turns out to be one of the best options, for it was that almost random testing that led the doctor in Paris—almost accidentally—to discover how well the drug that would become Sutent worked on kidney cancer.
So how to put ourselves where this kind of lightning will strike? How would we find out which trials were serious? Which kinds were duds? In which trials were patients seeming to recover? In which ones was nothing happening?
I remember Laura Lear, who posted as lmodrngrrl. The last post of hers that I read was very hopeful. She had gotten her boyfriend, Robert Cowen, the experimental drug Gleevec. His collecting duct kidney tumors were shrinking. He was feeling better. I hadn’t checked back on them since December 2002. How are they doing?
I searched out her name on the listserv. I saw his name and two dates in the subject line: Robert Cowen: October 26, 1959–September 9, 2003. I snapped the computer off and didn’t return to our search for several days.
So how did we eventually choose? How did we figure out which ones would work for us and which ones wouldn’t? We never really did. My notes show lists of phone numbers. Trial administrators. Doctors. Even drug company scientific representatives. Talking to them about the trials was tough. Officially they weren’t supposed to try to stack the deck, say, by encouraging people to join who look like they might benefit from the treatment—which is just what I wanted them to do. The needs of science came smack up against Terence’s and my needs. If it seemed the trial would benefit us, we would be more likely to join, and the results of the trial would perhaps look better than they should. That’s why so many of my questions along the way to the testers hit a brick wall.
So is this going to WORK? I demanded of each investigator, knowing full well the lunacy of the question. If they knew it would work, why would they conduct a trial? What I was really asking was: Does this have a chance? Does it make sense for us? Out of the hundreds of possibilities, why would we pick this one? Most of my queries were met with a polite official nonanswer and a faxed sheet of the study’s requirements. Quietly, though, every so often someone would nudge with just enough information to intrigue us.
In the end, one of the reasons we agreed so readily with Dr. Bukowski’s assessment that the best thing we could do was nothing is that we never did find anything—up to that point—that we thought seriously competed for our attention.
Behind the scenes, I learn many years later, horse trading does go on. Doctors know what their colleagues are up to; they know which trials are doing well and which are duds. When they have patients they think might benefit, they can steer them to the right place.
Of course, on the other hand, I find out years later that—just as we suspect—there is also huge pressure to recruit patients into one’s own clinical trial. And why wouldn’t there be? Clinical trials are a big business. They mean money for the institutions. Money for the doctors. Professional citations on research papers for the assistants. Professional advancement for the lead investigators. Not to mention the possibility of fame if the experiment succeeds.
Everyone along our journey seemed to be totally committed to their chosen role as healers. We thought they were good people. We trusted them. Yet it was impossible not to feel all those outside pressures as well.
Several years into our relationship with Dr. Bukowski, just such pressures crack—just a tiny bit—our feeling of solidarity with this man we have come to trust. At one of our regular meetings with him in Cleveland, on March 21, 2005, he asks us to participate in a clinical trial that he is conducting.
He leaves the room. A nurse, Sharon O’Keefe, enters with a consent form describing the trial:
An Ascending Single and Multiple Dose Study of the Safety, Tolerability Pharmacokinetics and Pharmacodynamics of HKI-272 Administered Orally to Subjects with HER2/neu or HER-1/EGFR-Positive Tumors
The drug is owned by Wyeth Research. Dr. Bukowski is listed as investigator. The topic is familiar. HER2/neu is a gene found in excess in aggressive breast cancers. Herceptin, a relatively new drug at the time, is being used to treat certain kinds of breast cancer. We know from earlier tests that Terence’s tumor, like many other kidney cancers, also shows signs of the HER2/neu gene. I even earlier got Terence approved to use a breast-cancer drug that worked against this gene. We begin to read the document. We are excited by what we read. The drug attacks this exact situation.
HKI-272 is an experimental drug. In laboratory studies, HKI–272 stopped cancer cells from growing by attaching itself to proteins called HER-2 and HER-1 which are members of a family of receptors found on both cancer and normal cells.
So far so good. Then, suddenly, our eyes meet. We have come to the same spot in the document … paragraphs four and five.
This is a Phase I trial of the experimental drug HKI-272 …
It is emphasized that the goal of a Phase I study is to measure toxicity, not response of your tumor. The primary objective is to find the maximally tolerated dose of the new drug.
A phase I trial? Measure toxicity? We read on. Each patient will take the drug at a different dose, to measure when the side effects become intolerable. Six cycles of the drug. Twenty visits to the Cleveland Clinic during the test—for blood tests, eye exams, questions about side effects, electrocardiograms, physical exams.
We read further. On page 6, the possible side effects are described: blood in the urine, decreased or no feces, hair loss, increased white blood cells, and lesions around the nose and/or mouth, diarrhea, nausea, vomiting, weakness, fatigue, fever, chills, headache, difficulty breathing … The list goes on and on.
Terence can barely stand the side effects of IL-2 when he thinks there is
a chance it can help him. We are stunned. Inside the examining room we say nothing. Outside, we confer.
“I don’t want to just be a guinea pig, goddammit,” Terence shouts, once safely in the car. “I want to get better.”
The clinic record for that day is terse:
Mar. 21—clinical presentation of study. KIRBY#6631 on HKI-272 for subjects with HER2/neu or HER-1/EGFR positive tumors. Reviewed with patient and wife. Financial responsibilities regarding procedures and medications discussed. Patient given copy of consent. Signed by Sharon O’Keefe, RN.
The United Healthcare record shows the clinic bills $138 for the visit. The records from Terence’s last meeting with Dr. Bukowski on December 19, 2005, simply note that since Terence has refused clinical trials at the Cleveland Clinic, the “best option” is to try one of the other trials.
Dr. Bukowski knows we are looking for treatment. He knows that we want to prolong Terence’s life. So why does he offer this trial?
In 2009, when I fly to Cleveland to meet the now-retired Dr. Bukowski at the clinic, I ask him just that question. Given that we had been coming to you looking to extend Terence’s life, why would you offer us a trial of a drug that would benefit the drug maker, maybe the hospital, possibly you, and—possibly—patients in the future, but not Terence himself?
“Because he was eligible for it,” says Dr. Bukowski.
That’s all he says. The conversation moves on. We turn to other subjects, but I am still not satisfied. At the end of the interview, I ask again. It’s one of the few really sore spots in our saga. I want to make sure that I know what he is thinking.
Why did you offer us this trial of something that wouldn’t help him? I ask again. I really want to know. I know Terence did too.
Because he was eligible for it, he says again.
Because he was eligible for it.
The trial he steers us to in January 2006 is different, though, almost the mirror image of the one we rejected in March 2005. This new one is a test of two compounds that are both known to be effective against kidney cancer. This trial will test whether the two drugs work better together than each does alone.
We jump at it.
18
From a distance, down the halls of Presbyterian Hospital in Philadelphia in January 2006, Dr. Keith Flaherty looks much bigger—and older—than he actually is. When he draws near we can see that he is not tall—a little more than midway between my five feet two inches and Terence’s five feet ten. From a distance his premature baldness gives him a dignified and statesmanlike air. When he comes closer we can see that he is considerably younger than either of us. We will later learn he is just thirty-five years old when we first meet him. When we ask him questions, he prefaces his answers with long pauses. At first we think he hasn’t heard, or is distracted, but we come to realize he is just framing careful answers.
When he talks, he gives the impression of having all the time in the world for us, something I later discover has been his hallmark ever since his student days. While Terence furiously scribbles on his index cards, Dr. Flaherty lays out the logic of the clinical trial Terence is about to join. Nexavar—also called sorafenib—is the first new drug to treat kidney cancer in more than a decade. On December 20, 2005, less than a month before our meeting with Dr. Flaherty, Nexavar was approved by the FDA after tests showed that it more than doubled the survival rate of those taking it. The co-lead investigator on that study, I will later learn: Dr. Bukowski.
So who is this Dr. Flaherty? More than two years after Terence’s death, a colleague, Ken Wells, and I spend hours visiting with him. Why kidney cancer? Why cancer at all? When he graduated from Yale in 1993 he thought of Wall Street. “I saw money for the sake of money and I saw medicine,” he says. “And I wasn’t sure which one I wanted.” The choice probably wasn’t really as hard as he makes it out to be: He’s the third child of two doctors—a psychiatrist and a cardiologist—the grandchild of another, and the spouse of yet another.
In medical school, what experience did he seek out? “I was focused on trying to find intensity and drama. I wasn’t trying to shy away, to go into ophthalmology or plastic surgery or some other boutique-ish profession that was about billing instead of illness. I wanted to take care of people who were ill or who were desperately afraid that they were.”
And when he got to the University of Pennsylvania hospital in 2002, what kind of cancer was he drawn to? “To be a renal cell specialist ten years ago was pretty grim,” he says. The only treatment available was the IL-2 that made Terence so ill in Lexington. Specialists at the hospital grouped cancers by their location, so one practice focused on kidney, bladder, testes, and prostate cancer. Of those, kidney cancer was the “least favorite” of one of his colleagues, because there was no hope. “My colleague was thrilled to give that to me: ‘Please, you deal with this. I don’t want it, thank you very much.’ ”
He began to work with new drugs. The kinds of drugs he now offers to Terence—drugs that attack the blood supply of the tumor, drugs that find the individual chemical signature that makes cells grow out of control. Drugs that target special pathways. He treated, he says, “if not the first, then the second” kidney cancer patient with Nexavar. He and a colleague in Chicago latched onto a “spaghetti against the wall” trial and tried Nexavar out on one patient each. “We said, ‘This is a drug that could work here.’ And sure enough, it did.”
To Dr. Flaherty, the shadows that Terence and I have chased for years weren’t shadows at all, but real colleagues and real trials. Before long, he and his Chicago colleague were treating 210 people in five places with Nexavar. “We just went kind of hog wild,” Dr. Flaherty says. Meanwhile, behind the scenes, others were testing what would later become Sutent.
“I call [a colleague] and say, ‘Bob, what have you got? Is there something that’s looking promising, something worth this patient making the trip up there once a month to be in a trial up there?’ We were perfectly honest about that. It’s clinical trials, but it’s really patient care. It’s not top secret stuff. It’s people with cancer we’re trying to help.”
He and others begin to realize that not just one, but many of these drugs were beginning to help people. “That was an exciting time: There are relatively few moments in medicine when you get the chill-up-the-spine kind of feeling—so much of what we do is a gradual day-by-day patient-by-patient process. This was a major leap forward.”
Cancer doctors do burn out, he says. All those funerals. All those grieving relatives.
It is the discovery that makes it all worthwhile.
“Burning out on this would be like burning out on life,” he says.
Dr. Flaherty has two young children and a weekend house in the Pennsylvania woods. He collects American first editions—a copy of V by Thomas Pynchon, a manuscript copy of Infinite Jest. He listens to Springsteen. Like Terence, he wears bow ties. Like Terence, he reads poetry. On his nightstand is Marvin Bell, an American poet most famous for his works “The Dead Man” and “The Dead Man Speaks.”
“The dead man is the only one who will live forever,” reads one of Bell’s poems.
Dr. Flaherty and Terence talk for hours about cancer. About the treatments. About cells and chemistry and the trials. Terence scribbles, scribbles, scribbles on his index cards.
“He had a very intellectual approach to his illness,” says Dr. Flaherty.
Nexavar, like many of the new drugs that were then still on the horizon, treats cancer by interrupting its ability to grow blood vessels to feed itself. Like an alien army marching across a fertile new territory, cancer builds supply chains to provide the nutrients to keep itself growing. Nexavar chokes off those supply chains. Without a way to tap into the bloodstream for food, the cancer withers and dies.
Avastin—bevacizumab—won’t be approved by the FDA to treat kidney cancer until August 2009, more than a year and a half after Terence’s death. But by the time we join the study, it is already clear that it too is effective agains
t the cancer’s blood-building pathways.
Dr. Flaherty explains the study’s rules: A tablet of Nexavar by mouth every day. An hour-long Avastin drip at the hospital every two weeks. Every month, a CAT scan of his chest to check on the size of the metastases. Terence and I are both eager to start. Dr. Flaherty’s notes from our first visit reflect this: Mr. Foley “expressed a strong interest in pursuing” the combination. “It will be several weeks before he can go on study, but the pace of disease continues to be slow and I think that this does not pose a risk to him.” United Healthcare pays $53.55 of the $118 charge for the visit. I don’t remember who paid the rest, but it must have been me.
We begin the trial at the end of February 2006.
We pick the Nexavar up at the pharmacy inside our Superfresh grocery store. Gino, the pharmacist, has to special order it. It’s not something he keeps on hand. Terence takes one tablet every day, 400 milligrams of the drug. Once a week, Terence drives across town from our rowhouse on the east side of Philadelphia and across the Schuylkill River to Presbyterian Hospital, a part of the University of Pennsylvania, on the west side of the city, where he sits and reads for an hour while he gets his Avastin drip. On March 28, 2006, he finishes his first four-week cycle and has his first CAT scans to see the results. Nothing much has changed.
Another month. Another cycle. Another CAT scan. Same results. At least the tumors aren’t growing anymore, we think. But by June 2006, the fourth month of the trial, the scans have a new story to tell. Not only are there no new lesions in his lungs, the biggest of the original ones have begun to shrink. They are so much smaller, in fact, that Dr. Flaherty’s notes pronounce Terence a confirmed “partial response”—meaning that the metastases are now at least a third smaller than they were when we began.
The Cost of Hope Page 14
