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Sorting
out the Hype and Hope of Targeted Therapies Dean
Gordanier is a tax lawyer, fitness buff, father of three and, at age
54, a veteran of the roller-coaster ride of hope and despair that is
becoming a way of life for growing numbers of people with cancer,
thanks to the promise, and the heartbreak, of a new generation of
cancer drugs. Many of
these drugs, which oncologists call “targeted therapies,” are
breathtaking scientifically. With names like Gleevec, Avastin,
Iressa, Rituxan, Herceptin, even the still-nameless drug known as
SU11248, these drugs are the closest scientists have come yet to the
holy grail of cancer treatment – knocking out cancer cells with
great specificity without wreaking too much havoc on the rest of the
body. Some of
these drugs target specific enzymes called kinases that act as
switches that control cell functions; in some cancer cells, kinases
are locked in the “on” position. Others are monoclonal
antibodies that attack markers
on the surface of cancer cells. And some starve tumors of blood
supply by attacking proteins that make blood vessels grow. “I am
so unbelievably excited about the science because it is like
standing on the Nina, the Pinta or the Santa Maria. You can see the
New World coming,” says Dr. George Demetri, director of the Center
for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in
Boston. Gordanier
is excited, too, as well he might be, since these drugs have saved
his life – twice. But he is wary as well. Like any seeming miracle
treatment, targeted therapies are fabulous if, and while, they work.
But because cancer cells are wily and can mutate to escape a
drug’s action, even the most promising drug may stop working after
a while. In the
fall of 1999, Gordanier went to his doctor complaining of acid
indigestion. Two days after Christmas, he had tests that showed a
grapefruit-sized lump in his belly. It turned out to be a
potentially deadly kind of stomach cancer called GIST
(gastrointestinal stromal tumor). In early
January, 2000, Gordanier signed a consent form “acknowledging that
life is uncertain and evisceration has its risks,” as he wryly put
it in his diary, and underwent a drastic form of surgery called a
“Whipple” in which doctors removed the tumor, 90 percent of his
stomach, his spleen, 70 percent of his pancreas and his transverse
colon. But by
September, his pain- and his cancer – were back. Doctors tried
chemoembolization, or squirting chemotherapy drugs directly into the
blood supply of his tumors, which had now spread to his liver. It
didn’t work. In late February and early March of 2001, he simply
“waited to die,” as he wrote in his diary. Then he
got lucky, joining a clinical trial of Gleevec for GIST. (In May,
2001, the US Food and Drug Administration approved Gleevec for
chronic myeloid leukemia. The FDA went on to approve Gleevec for
GIST in February, 2002.) “I have
been saved by the bell,” Gordanier wrote in his journal. “It
looks like Gleevec will allow me to struggle on with a good
possibility of a successful outcome, if you define success (as I do)
as being able to live and work without pain and to enjoy each day as
it comes and for what it brings.” But 18
months later, by December, 2002, Gleevec had stopped working, as it
does in about 75 percent of people after two years. Once
again, death loomed perilously close until Gordanier’s doctor
referred him to Demetri. Demetri suggested SU11248, an experimental new drug also called Sugen, for the
company that developed it. (It is now made by Pfizer.) Since
mid-January, Gordanier has been taking SU11248. So far, it’s
working. “It’s
a holding action,” says Gordanier. “The cancers will mutate. But
I will be alive as long as the doctors can keep one step ahead of
the tumors.” As
Gordanier and others with life-threatening illnesses have learned
the hard way, it’s crucial to ask questions about any new drug,
even an apparent wonder drug that sounds like the best, or only,
option. “With
any kind of experimental drug, you want to know two things: how
likely is it to help, and what kind of harm can it cause?” says
Gordanier. “If the likelihood of buying more time is low and
severe side effects are a real possibility, it’s hard to decide
whether to risk whatever good weeks or months you have left- no
matter how desperate you are.” For
instance, even when a new drug is successful by statistical
standards, the impact in real life may be minimal. Avastin, for
instance, garnered big headlines at the recent meeting of the
American Society of Clinical Oncology because it proved an important
principle: That blocking a tumor’s blood supply can slow tumor
growth. But the drug only prolongs life for an average of five months in colon cancer patients. Whether that is a lot or a little “depends on what the five months are like. Is the five months likely to be spent in the intensive care unit of a hospital or at home?” asks medical ethicist Dr. Walter Robinson, a pediatric pulmonologist Boston’s Children’s Hospital. Patients should also ask doctors to explain carefully the figures they quote from studies. Usually, such figures are averages, which means that if a drug prolongs life by five months on average, some people may get 10 months or more, some barely any. And if
you’re basing your decision on results of a few specific studies,
ask exactly what those studies measured, cautions Dr. Sidney Wolfe,
director of Public Citizen’s Health Research Group, an advocacy
group in Washington, D.C. “You
really want to know whether the drug is effective for treating the
condition you have, not some surrogate end point. Lowering blood
pressure doesn’t count unless it decreases stroke,” he says. It
may not be compelling for a drug “just to shrink tumor size
temporarily if it’s not accompanied by increased survival.” Ask about
side effects, too, though with very new, experimental drugs, doctors
may not know much. Rita Raj, a women’s health advisor to the
United Nations in New York, has taken Gleevec for stomach cancer,
like Gordanier. Her tumor appears to have disappeared, she says, but
she has had side effects, chiefly fluid retention and kidney
failure. “Be
extremely proactive,” adds Cyndie Mc Lachlan, 63, a philanthropist
from Lopez Island, Wash., who was given one to three months live
when she was diagnosed with advanced lung cancer nearly two years
ago. She has been taking Iressa and seen the
tumors in her lungs and brain shrink dramatically. The
bottom line for patients like these is that these new drugs,
imperfect as they still are, can buy time - time in which still
newer, and possibly better drugs, may be found. “I’m
feeling good each day, and new drugs are in the research pipeline,
but nothing is certain,” says Gordanier. “I’m still doing my
best to live my life one day at a time.”
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