I n 2004, free of cancer for five
years, Chicago undercover detective Jim Smith thought
he’d beaten
the odds. But a year later, at age 53, Smith could
think only of death. His colon cancer, treated with
surgery, radiation and chemotherapy in 1999, had
returned, metastasizing to his lungs with 14 new
tumors.
Smith agreed to more chemotherapy. This time his
doctor added a drug designed to disrupt the tumors’ fuel lines,
the blood vessels supplying oxygen and nutrients. By the fourth treatment,
a CT scan showed the tumors were shrinking. But the best news came a few
months later, after a car accident landed Smith in the hospital. “I
was getting another CT scan, and I told the trauma doctor he would see
spots on my lungs,” says Smith. “He said, ‘What spots?’ There
weren’t any.”
With Smith’s metastatic cancer in full remission, his doctor, Mark
F. Kozloff, director of oncology at Ingalls Hospital in Harvey, Ill.,
stopped the chemotherapy. But Kozloff is keeping Smith on a $7,000-a-month
maintenance dose of Avastin (bevacizumab), a drug that targets the tumors’ vascular
infrastructure. That should help keep the cancer at bay for a while. “Adding
Avastin has stretched survival time for metastatic colon cancer to well
over 20 months, from 17 months with chemotherapy alone,” Kozloff
says.
A drug that extends life by mere months may not sound
like a big deal. But to many oncologists, Avastin’s potential seems
huge. “You could say, ‘What is all the hype about? Avastin
simply delays the ability of tumors to kill,’” says Mark W.
Kieran, director of pediatric medical neuro-oncology at the Dana-Farber
Cancer Institute in Boston. “Or you could say, ‘My God, we’ve
finally found a new way to take us beyond the dent we’ve made in
cancer with chemotherapy and radiation alone.’”
Though only approved by the Food and Drug Administration
for first-line treatment of metastatic colorectal cancer in combination
with chemotherapy, Avastin is proceeding through more than 100 clinical
trials involving thousands of patients with many kinds of cancer. Researchers
hope to prove it can keep cancer from recurring after an initial round
of successful treatment. “With surgery, radiation and chemotherapy,
you try to get out all of the cancer, but there may be stray tumor cells,” says
Patricia M. LoRusso, professor of medicine at the Barbara Ann Karmanos
Cancer Institute in Detroit. Those cells are potential metastases. “If
you can keep the cells dormant by preventing them from establishing a
blood supply, you may be able to keep the cancer from ever coming back.”
In that scenario, patients likely would have to stay
on a lifetime regimen of Avastin (or some combination of related compounds),
much like the cocktails that have helped transform AIDS into a treatable
chronic disease. That’s the potential of Avastin and an emerging
class of similar drugs—that cancer, too, could become manageable.
It would be the ultimate validation of a long-ridiculed theory first proposed
40 years ago.
As a young surgeon during the 1960s, Judah Folkman,
now director of the vascular biology program at Children’s Hospital
in Boston and professor of pediatric surgery and cell biology at Harvard
Medical School, noticed a peculiar distinction between the large cancerous
tumors he excised from patients and the microscopic tumors in dog thyroid
tissue he was studying in the lab. The large ones were entangled in wild
nests of blood vessels, while the minuscule ones had no blood supply and
were apparently dormant. Folkman wondered whether the active tumors were
secreting something that generated the profusion of blood vessels. And
if so, whether there was a way to inhibit the process.
The creation of blood vessels, known as angiogenesis,
was only cursorily understood. It occurs during the menstrual cycle to
rebuild the uterus, and during pregnancy to form the placenta, and children’s
bodies depend on it to nourish growing tissues and organs. Get a deep
cut, and your body produces angiogenic growth factors, proteins that activate
normally quiescent endothelial cells lining blood vessel walls. The vessels
form capillaries to ferry oxygen and nutrients to the damaged tissue.
Once healed, the body somehow turns off its angiogenesis switch.
When Folkman proposed that angiogenesis might play
a crucial role in cancer, most researchers were focused on the possibilities
of chemotherapy. Folkman’s 1971 publication of a paper in the New
England Journal of Medicine outlining his hypothesis was greeted with
considerable ridicule. Many colleagues felt it was premature, and basic
scientists noted that Folkman was a surgeon, not one of them. Few wanted
to work in his lab, and at first he found it difficult to obtain grants. |
