The Cost of Hope (18 page)

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:

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.

So far so good. Then, suddenly, our eyes meet. We have come to the same spot in the document … paragraphs four and five.

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:

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.

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 against 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.