[The quote from Dr. Leonard Saltz about the effect of the warning on off-label use basically echoes the remarks in #msg-3800593. (It’s nice to be in such renowned company.)]
Cancer Drug Apparently Doubles Risk of Blood Clots Linked to Heart Problems
By DAVID P. HAMILTON Staff Reporter of THE WALL STREET JOURNAL August 16, 2004
Genentech Inc. warned doctors and the Food and Drug Administration that its new colon-cancer drug Avastin appears to double the risk of blood clots related to stroke or heart problems, an unexpected development that might crimp wider use.
Recently pooled data from five controlled clinical trials showed that 5% of patients taking Avastin in combination with an older chemotherapy drug called 5-FU developed a "serious" type of arterial clotting, roughly twice as many as those whose treatment didn't involve Avastin, the company said in a letter to doctors.
The risk of death from clot-related stroke and heart problems also increased, according to the letter. Genentech, the world's oldest biotechnology company, said it couldn't be more specific because it is still vetting that analysis with the FDA.
Genentech and cancer doctors said the warning won't necessarily affect existing use of the drug, which was approved last February for the treatment of metastatic colon cancer. The company, for instance, emphasized that those most at risk of dangerous arterial clots appear to be patients over 65 years old who have previously had clotting problems.
Avastin had been linked to clotting problems, although until now those side effects weren't considered as common or as dangerous as the possibility of hemorrhage or perforation of the colon. Genentech, of South San Francisco, Calif., said it is in the process of revising its warnings for the drug in consultation with the FDA. In its letter, it said that patients who experience arterial clotting during Avastin treatment should discontinue the drug permanently.
"This is a cause for caution, not panic," said Leonard Saltz, a cancer specialist at Memorial Sloan-Kettering Cancer Center in New York. Cancer doctors will need to be aware of the risks and watch for possible clot-related complications, he said, but they should also remember that colon-cancer patients still tend to live longer when treated with Avastin.
But Dr. Saltz said he would be wary about using Avastin outside of its approved indication, a common and legal practice among cancer specialists. Many cancer researchers, for instance, hope that Avastin might also work as a so-called adjuvant treatment, which is chemotherapy designed to prevent surgically removed tumors from recurring. Dr. Saltz, however, warned against prescribing Avastin as an adjuvant until clinical-trial data show that its benefits outweigh its risks.
Genentech plans to begin such a trial later this year and will likely modify it somewhat in light of the latest warning, a company spokesman said.
Avastin is a new type of cancer drug designed to starve tumors by blocking the formation of blood vessels that carry vital oxygen and nutrients; it has been widely hailed in the medical and financial communities. It is the first drug of its type to extend life in cancer patients, and extravagant hopes for its commercial success helped Genentech shares soar this past spring. Since June, however, the company's stock has steadily lost ground amid a general decline in cancer-related biotechnology shares, with its price falling by almost a third since its peak.
Following release of the Avastin warning letter, Genentech shares dropped $2.88, or 6.1%, to $44.23 as of 4 p.m. Friday in composite trading on the New York Stock Exchange. The stock regained some ground in after-hours trading.
David Ross, deputy director of the FDA office of drug evaluation VI, said clotting problems in earlier trials appeared in "relatively small numbers" and "didn't rise to the level of a warning." But in July, the company showed the agency new data from older, frail patients that confirmed there was a broader problem. <<
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