Mixed Results for a Cancer "Cure"


By Catherine Arnst A substance prematurely heralded three years ago as a cure for cancer has shown only limited evidence of success in its first human trial. In a report to the American Society of Clinical Oncology in San Francisco, researchers said that Endostatin, made by Entremed, caused significant tumor shrinkage in only 2 of the 25 patients tested, and that the cancer eventually grew in all the patients. However, the researchers, from M.D. Anderson Cancer Center in Houston, were encouraged by the discovery that the drug did stop blood-vessel growth to the tumors, as it was designed to.

Endostatin gained worldwide attention in 1998 after front-page New York Times story reported that the drug had stopped tumor growth in mice and might be the long-sought "cure" for all types of cancer. The news was picked up around the world and heralded on the cover of magazines.

STARVATION STRATEGY. Entremed's stock skyrocketed before -- reaching a peak of $101 last summer -- the company and Dr. Judah Folkman, the Harvard scientist whose lab discovered the compound, were able to dampen enthusiasm by pointing out that Endostatin was still in extremely early stages. Yesterday, Entremed closed at $15.30 after dropping $3.95 on the day.

Endostatin is one of a class of compounds meant to stop blood-vessel growth to cancer cells, essentially starving tumors to death. Folkman had discovered that angiogenesis, or blood-vessel growth, occurs only three times in the adult body -- during pregnancy, menstruation, and when tumors grow. Folkman figured that stopping angiogenesis, you could deny tumors the blood they need to thrive and spread.

Endostatin serves as an example of how difficult it can be to turn a lab discovery into a drug. Though Folkman's lab had shown remarkable results when using Endostatin on cancer-ridden mice, it was many months before the National Cancer Institute and others could replicate those results-- a prerequisite before any human trials.

QUALIFIED GAINS. The M.D. Anderson trial began in November, 1999. All the patients selected had different types of solid tumor cancers that had failed to respond to conventional treatments.The Phase 1 trial was designed to test the safety of dosing only. But because of the intense interest in Endostatin, the results attracted enormous attention at ASCO, one of the largest cancer meetings in the world.

Alas, all of the patients showed at least some evidence of disease progression. But Dr. Roy Herbst of Anderson, the lead investigator on the study, says he considers the trial a success. The reason: PET-scan imaging showed increasing doses were associated with decreased blood flow to tumors, proving the principle behind Endostatin.

Also, the drug was well tolerated by patients even at the highest doses given -- 300 milligrams per day administered intravenously. The results, Herbst said cautiously, suggest that Endostatin may have a role in the treatment of cancer.

Herbst was careful not to hype the much-publicized drug, but he ended his presentation by paraphrasing Winston Churchill: "This is not the beginning of the end, but it may be the end of the beginning." Arnst, who covers medicine and science for BusinessWeek, is attending the conference in San Francisco


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