The Cancer Chronicles (24 page)

It was during this time that we drove on a Saturday afternoon to the campus of the New Mexico School for the Deaf where the
American Cancer Society was holding its
Relay for Life. People with cancer are no longer called patients or victims but
survivors, and they walked proudly around the track wearing blue T-shirts with a big star and the word “HOPE” in capital letters. (Nancy had another T-shirt at home that said “Not Dead Yet.”) I’ve saved five pictures from then. She is wearing black shorts or a midlength skirt—I can’t tell for certain—and I see that her right leg is already swollen with
lymphedema. We were assured that it was probably a temporary side effect of the surgery—from damaged lymph vessels—and aggravated perhaps by the treatment. But the swelling never went away. It wasn’t such a bad compromise, she would say, for being alive.

Her plan had been to rip off her hat during the procession, bearing her bald
head in celebration of having endured the surgery, the chemo, and the first sessions of radiation. But the moment never seemed right. The most memorable part of the day came as the participants walked one by one to the stage, where they briefly introduced themselves, and the first lady of New Mexico bestowed them each with a gold medal and purple ribbon. “I am a cancer survivor,” the first woman said, and then the next and the next. I thought of how we’ve come to sugarcoat our afflictions. Deaf becomes “hard of hearing” becomes “hearing impaired”—and then loops back full circle with the embrace of Deaf Community and even Deaf Culture. Now there is a cancer culture, and whether you had a harmless in situ carcinoma removed with a simple lumpectomy or are fighting the terminal stages of metastatic melanoma, you are called a survivor. In the first case there was nothing to survive. In the second case there will be no survival. The word has been all but stripped of meaning. My thoughts were interrupted when a tall, thin woman with a chemo scarf grabbed the microphone and proclaimed: “I am a
second-time
cancer survivor.” Was that really something to celebrate? That the cancer had come back again.

On the early morning flight from Albuquerque to Boston, the captain was wearing a
pink tie, and a pink kerchief was peeking from the pocket of his uniform. The flight attendants were similarly dressed, with pink shirts and aprons. It was
National Breast Can- cer Awareness Month, and when the plane was in the sky one of the attendants enthusiastically announced that the airline was selling pink lemonade and pink martinis—this on a flight departing at 6 a.m. The proceeds would go for “curing” breast cancer.

No more than a hundred years ago cancer was a word spoken only in whispers lest the illness be stirred from its slumber. One might die of “heart failure” or “
cachexia,” a latinized way of saying that, eaten by cancer, a loved one had wasted away. Though the
fear has not disappeared, “cancer” is no longer the unutterable word. The cheerfulness with which the subject has been embraced and shouted is almost macabre. A cosmetics company was advertising “
Kisses for the
Cure.” Buy a lipstick and a small donation would be made to the fight. “Pucker up and Kiss Breast Cancer Goodbye.”

As I paged through the airline magazine, I thought of the
Stand Up to Cancer telethon I’d watched a few weeks earlier, with singing,
laughing, and sometimes somber
celebrities vowing to “eradicate”
cancer of all kinds. Not control it or reduce it or treat its occurrence more effectively. “Someday no child will die from cancer,” a buoyant teenaged actress promised. Not a single one. “We must beat it back and beat it out of existence,” said
Stevie Wonder, hunched over a piano. His first wife had died from cancer, and many of the other stars had also been closely struck.
“Cancer doesn’t care that you’ve won the Olympic gold medal. Cancer doesn’t care if you’re beautiful or brilliant or just starting college.…”
One by one in their “Cancer Survivor” T-shirts, the idols and their idolizers took the stage.
“Cancer doesn’t care if you have your whole life in front of you.…Cancer doesn’t care that you have young
children who need their mother.…Cancer doesn’t care that it just took your father.
…
It just doesn’t care.”
A ticker tape message scrolled across the bottom of the TV screen: “Cancer Doesn’t Discriminate.” But it does. Against the elderly, the obese, the poor. Demographically the young, beautiful people on the show were exceptions. But who could resist their good hearts and cheer? “The stars are taking your calls.” And so the telephones rang, the pledges poured in. At the end of the show a procession of scientists filed across the stage to a rousing chorus of “You’ve got to
stand up, stand up, stand up
to cancer.…” Altogether more than $80 million was raised that night.

Stand Up to Cancer is a respected organization reputed to funnel almost all of the money it collects to research. But I wondered if the viewers, as well as the performers, had been left with false hopes. The donations, it was said, would go to “dream teams” of scientists cooperating on a cure instead of competing for recognition and grant money—as if only greed and egos stood in the way of understanding the most
complex of medical phenomena. Comparisons were made to
Jonas Salk and the
March of Dimes, yet
polio had been a vastly simpler problem—a disease with a single cause that could be isolated and vaccinated against.

Understanding cancer will require no less than understanding the deepest workings of the human cell. One performer invoked
the fight against slavery and the triumphs of the civil rights movement. “What if no one stood up for freedom on the Underground Railroad … if no one was standing up for injustice at a bridge in Selma?”
Cancer was something to demonstrate against or to oppose with a sit-down strike. These didn’t seem like people who were apt to engage in mass acts of civil disobedience like those of
ACT UP, the AIDS Coalition to Unleash Power, whose influence lay in its obnoxiousness. Two decades ago, ACT UP demonstrated against the
National Institutes of Health and shut down the
Food and Drug Administration for a day, demanding more research money and affordable treatments. One way or another more attention became focused on the problem. Now AIDS can be managed as a chronic disease. But not even
HIV is as convoluted as cancer.

Descending toward Boston, the plane provided a bird’s-eye view of what vies with MD
Anderson as the most powerful cancer center in the world. On one side of the river were
Dana-Farber,
Beth Israel Deaconess, and
Massachusetts General Hospital. On the other side were the
Whitehead Institute, the Broad Institute, and the campuses of
Harvard and MIT. With their petri dishes, gas chromatographs, gene sequencers, and electron microscopes, researchers in these few square miles produce a staggering amount of knowledge about the intricate connections inside a human cell and how they can come undone. For all the horror it causes, cancer is a fascinating intellectual problem—a window into understanding life. But only very slowly do the new findings make their way to hospital clinics, where people are being treated with
chemo and
radiation—techniques not much less brutal than what
Solzhenitsyn described in his novel
Cancer Ward.
The dream teams were trying to cross the divide.

This was part of a broader effort called
translational research, which was the subject of
a workshop that evening at the Parker House, the grandest of Boston’s old hotels. In a room with chandeliers and wainscoted walls, I sat among a group of young scientists who were learning about the different cultures of medical research: biologists who study the chemical cascades inside a cell, clinicians
who develop and test new
drugs, oncologists and the patients they are treating—they all see cancer in different ways. While the mornings would be filled with lectures, in the afternoons the students would visit cancer clinics and hospital pathology laboratories and watch over a medical ethics panel as it reviewed the rules for conducting new clinical trials—an arena in which the priorities of science and medicine often conflict.

Amy Harmon, a reporter for
The New
York Times,
had recently
told the story of two
cousins with advanced
metastatic melanoma, which is about as deadly a cancer as you can get. Both young men—they were in their early twenties—were accepted into a trial for a
targeted therapy,
vemurafenib, which promised to shrink tumors that were driven by
a mutation in a gene called
BRAF.
A small Phase I trial and a larger Phase II had shown promising results. Now it was time for Phase III—675 people in twelve countries—the last step before seeking approval from the FDA.

That is where the dilemma arose. The cousins were lucky to be in the trial—only about half of melanoma cases have this particular mutation. But one of them,
Thomas McLaughlin, was randomly assigned to the experimental group, which would get the new therapy (“the superpills,” he called them) while the other,
Brandon Ryan, was in the control group, which would get
dacarbazine, the standard and depressingly ineffective
chemotherapy. Both men were dismayed by the arbitrariness of the decision. McLaughlin, whose melanoma was already Stage 4, wanted to switch places with Ryan, whose somewhat less advanced malignancy might have given him a better chance. But that was not allowed. It would compromise the objectivity of the trial.

It was a heart-wrenching story with the good of the few bowing before the good of the many. Without rigorous comparisons like these there might be no new drugs for anyone. Still, it was hard not to think of the people in the control group as sacrificial lambs. Medical ethicists use the term “
clinical equipoise” to describe a trial in which there is no a priori reason to consider one treatment superior
to another. Only then, many argue, is it right to decide blindly which patient will get which drug. By the time Phase II had ended, vemurafenib appeared to blow dacarbazine out of the water, yet half the patients would now be getting what already seemed like an inferior treatment.

In the end,
Phase III proved so definitive that it was interrupted early so both groups could benefit. Initial reports showed that vemurafenib increased progression-free survival, holding the
cancer in abeyance for 5.3 months, compared with 1.6 months for dacarbazine. That was enough for the FDA. Before long the drug was approved and being marketed by
Genentech. At last report patients were
typically living four months longer than those on dacarbazine.

There was no happy ending. Ryan, the cousin in the control group, was among the many who had died during the first year of the trial—
sixty-six in the dacarbazine group and forty-two among those getting vemurafenib. By the time another year had passed
half of the people who had enrolled in the study were dead. McLaughlin’s tumors had spread throughout his body, from his thighs to his brain. But he was still alive and taking the superpills. He told me he was back at his job as a welder, working in the sun. I thought of a passage in
Cancer Ward:
“All the time
he was running a race against the tumor to come, but racing in the dark, since he couldn’t see where the enemy was. But the enemy was all-seeing, and at the best moment of his life it pounced on him with its fangs. It wasn’t a disease, it was a snake. Even its name was snakelike—
melanoblastoma.” That is an older name for McLaughlin’s cancer.

For advanced metastatic melanoma there is nothing that resembles a cure. No matter what the treatment, the aberrant cells discover,
through a fortuitous mutation, how to continue with their expansion. Vemurafenib also has
a paradoxical side effect: encouraging the growth of other
skin cancers,
squamous cell carcinoma and
keratoacanthoma.
Researchers are
experimenting with combinations of targeted therapies that aim to overcome these obstacles, hoping that the cancer cells won’t develop yet another workaround.

One of the aims of translational
research is to bring scientists out of the laboratory so they can see firsthand what patients are going through. At the Parker House,
Tom Curran, a professor of pathology at the University of Pennsylvania medical school,
described the jarring
effect of moving from the isolation of a pharmaceutical company laboratory to St. Jude
Children’s Research Hospital in Memphis, where he took a job in 1995. Curran had
discovered a gene called
reelin,
which helps direct the migration of neurons during the early
development of the brain, including the
cerebellum. The cerebellum is the center of muscular control and balance, and
mice born with defects in the gene walk with a reeling gait. Mutations in developmental genes are also responsible later on for many pediatric
cancers, and Curran was particularly interested in
medulloblastoma, an aggressive cancer of the cerebellum. Compared with other cancers it is extremely
rare: the prevalence among adults is
8 cases in 10 million. But there are
5 cases per 100,000 among children and teenagers, making it
the most common pediatric brain tumor. The
median age of diagnosis is five. What might begin as nothing more alarming than flulike symptoms can give way to headaches and vomiting, dizziness, loss of balance, and what has been described as “
a clumsy, staggered walking pattern.”

For Curran, medulloblastoma had been mostly an abstraction until he met children who were being treated for the disease. He knew that for most patients the prognosis was relatively good—
the five-year
survival rate was as high as 80 percent. For some patients, however, the cancer is recurrent and fatal. Even when the treatments are successful, the side effects can be ruinous.
Surgery is usually followed by radiation beamed into the vulnerable brains of children.

“
I met one kid, a teenager, who was more than five years free of his disease,” Curran told the audience. “He was about sixteen. He was blond haired, blue eyed. He was joking around with the physician. But he was beginning to realize that the rest of his class was continuing to advance and he was leveling off. He began to see that the rest of life was going to be a terrible struggle for him and his
family. Working in the lab doesn’t give you that kind of perspective. I couldn’t get the images out of my head.”