New drugs starve cancer tumors

Target: Synthetic antibodies are going on the market, substances that interfere with the blood supply to malignant cells.

Medicine & Science

March 08, 2004|By Judy Peres | Judy Peres,CHICAGO TRIBUNE

Two revolutionary new drugs are in hospital pharmacies this week, a tangible sign that years of research into targeted approaches to fighting cancer are finally paying off, at least in a limited way.

The new drugs are a far cry from the breakthrough that was predicted in 1998, when Nobel laureate James Watson was quoted as saying cancer would be cured "in two years" as a result of laboratory evidence that tumors would vanish if their blood supply was choked off.

Nevertheless, Avastin, approved Feb. 26 by the U.S. Food and Drug Administration for treating advanced colon cancer, works precisely that way: It starves cancers by depriving them of the nutrients they need to grow and spread.

A synthetic antibody developed by Genentech, Avastin was the second targeted cancer drug to be approved in two weeks. On Feb. 12, another antibody, Erbitux, won FDA clearance for a later stage of the same disease. (Erbitux, developed by ImClone Systems, is the drug at the heart of the Martha Stewart stock-trading scandal.)

"These drugs add to the growing list of new, specifically targeted treatments [that are] effective, less toxic and useful in a host of different cancers: breast, lung, colon and others," said Dr. Robert Mayer of Boston's Dana-Farber Cancer Institute. "None of this was there five years ago. It's incredibly exciting."

The two drugs, and numerous others recently approved or in development, are part of a sea change made possible by new insights into the molecular biology of cancer. Unlike conventional drugs, which kill normal cells along with cancerous ones and have toxic side effects, the new drugs block cellular mechanisms that promote cancer.

"We're in a new era of drug development for cancer," said Dr. Hedy Kindler, director of gastrointestinal oncology at the University of Chicago, who has tested Avastin and Erbitux.

Kindler is running two clinical trials, in colon and pancreatic cancer patients, in which the two drugs are combined. She and others are also testing Avastin in other diseases, including cancers of the breast and lung, and mesothelioma, an asbestos-related cancer.

"The next step will be to move these drugs into patients with earlier-stage disease that may be more curable," Kindler said.

Drugs such as Avastin and Erbitux should be able to destroy the cancer while sparing the body's normal systems. Patients taking targeted drugs typically do not suffer the hair loss, stomach upset, mouth sores and loss of infection-fighting white blood cells that accompany conventional chemotherapy.

Only one new drug has been able to cure cancer patients on its own. That drug, Gleevec, attacks a mutant protein found almost exclusively in patients with chronic myeloid leukemia.

But most other cancers - especially the big killers, such as breast, prostate, colon and lung cancer - involve numerous mutations. Scientists now believe that targeting any single genetic abnormality won't be enough and that the main role of the new drugs will be in combination with other agents.

The excitement in the field of colon cancer is especially great because the two new drugs target different molecular paths.

Avastin blocks VEGF, or vascular endothelial growth factor, which tumors need to grow new blood vessels. Erbitux works by blocking another pathway, EGFR, or epidermal growth factor receptor.

Cancer of the colon or rectum is the third-most-common cancer in the United States and the second-leading cancer killer. About 147,500 new cases were diagnosed last year.

Avastin was tested along with the standard cocktail of chemotherapy agents used for colon cancer that has already spread to other parts of the body. Patients who got Avastin lived an average of five months longer than those who got a placebo.

Erbitux, too, is administered with standard chemo, but it might be given alone to patients who can't take the standard drugs. It's not known whether it can extend patients' lives, but it did shrink tumors or delay tumor growth in clinical trials.

It's not clear yet how much these drugs will cost patients. The wholesale cost of Avastin is $4,400 a month. Erbitux is $9,600 a month wholesale, but patients are likely to take it for a shorter period.

Avastin is the first anti-cancer drug that works by blocking the growth of new blood vessels.

Dr. Judah Folkman of Children's Hospital in Boston theorized more than 30 years ago that tumors would starve if they didn't have blood vessels to provide oxygen and other nutrients. The theory worked in laboratory mice but until recently was unsuccessful in humans.

The Chicago Tribune is a Tribune Publishing newspaper.

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