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A FOUR DECADE QUEST TO SHRINK TUMORS:
The establishment scorns one man’s discovery // Research languishes for lack of funding // Momentum is lost with human-trial failures // A life-changing drug cocktail arrives at last.

Turning Off Cancer

By Anita Slomski // Illustrations by Leif Parsons // Spring 2006
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In 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.

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Too Many Blood Vessels—Or Too Few

Some 60 diseases are linked to the excessive or restricted formation of blood vessels. Here is a sampling of research, at various stages, into flipping the angiogenesis switch on or off.

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hed-dossier

1. Dr. Folkman’s War: Angiogenesis and the Struggle to Defeat Cancer, by Robert Cooke [Random House, 2001]. A highly readable account of the obstacles and skepticism Judah Folkman faced in proving his theory.

2. “Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy,” by Rakesh K. Jain, Science, vol. 307, Jan. 7, 2005. Beautifully illustrated article on the response of tumors to antiangiogenic therapy.

3. “Insight: Angiogenesis,” Nature. Special supplement on the role of angiogenesis in disease and medicine.

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