Drugs That Block Cancer Blood Supply Show Promise and Danger (dateline June 2, 2000)
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Preliminary studies using drugs called angiogenesis inhibitors show promise in treating advanced (metastatic) breast cancer as well as advanced lung and colon cancers. Researchers believe angiogenesis inhibitors work by cutting off the blood supply to cancerous tumors, preventing the tumors from growing larger. However, the drugs may have dangerous consequences: four lung cancer patients died suddenly after they experienced bleeding in their tumors. The media coverage devoted to the discovery of two compounds, angiostatin and endostatin, by Judah Folkman, MD in 1998 has sparked widespread interest in angiogenesis inhibitors. In animal studies, the drugs have had a significant impact on the progression of cancer, but similar results have not yet been produced in humans. However, several small reports on angiogenesis inhibitors at the annual meeting of the American Society of Clinical Oncology (ASCO) meeting show that the compounds may slow the progression of cancer in some breast, lung, and colon cancer patients. Results have been less favorable with other types of cancer, such as metastatic head and neck cancers. One class of drugs reported on at the ASCO meeting, called anti-VEGF compounds (vascular endothelial growth factor), block a cancerous tumor’s use of VEGF—a substance that enables tumors to grow new blood vessels and repair old ones. By cutting off the tumor’s blood supply, the drugs may be able to shrink the tumor to the size of a pinhead. Though the results have not been as dramatic as in animals, researchers have been pleased that the anti-VEGF drugs are helping to shrink tumors in some patients, at least for a few months. Larger clinical trials will determine how long the drugs can slow down disease progression or if anti-VEGF compounds could actually be used to eliminate cancer from the body. Currently, the anti-VEGF drugs have been used alone or in combination with other chemotherapy drugs. Serious Side Effects As researchers are learning
more about the possible benefits of angiogenesis inhibitors, they are also discovering the
serious side effects of the drugs. In one study of an anti-VEGF drug
developed by Genentech, Inc., the maker of the breast cancer drug,
Herceptin, six of the 99 lung cancer patients who
were given the drug developed sudden bleeding in tumors in their lungs. Four of those patients died. All of the affected patients
had a certain type of advanced non-small-cell lung cancer called squamous cell carcinoma. While researchers are not certain why these
patients developed fatal bleeding, a possible explanation is that the anti-VEGF drug
destroyed blood vessels near the tumor that had been supporting lung tissue. Though the deaths from the
anti-VEGF drug were unfortunate and surprising, the researchers say that bleeding could
show that the drug is truly working, disrupting the tumor’s ability to retain a blood
supply. Bleeding was not seen in patients
with breast, colon, or other types of cancers. Other
potential side effects of anti-VEGF drugs include high blood pressure and blood clots. Additional clinical trials on
anti-VEGF drugs are planned for advanced breast, lung, and colon cancer patients. Preliminary human studies on the drug endostatin are currently underway. While researchers have not commented whether
endostatin has shown the ability to cut off a tumor’s blood supply in humans, Dr.
Folkman, who discovered endostatin, told physicians at the ASCO meeting that he is
“very pleased” with the early results of the studies. Additional Resources and References
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