Early Report Shows Endostatin No Magic Bullet Against Cancer

      A dose of reality was delivered Monday to those who had hoped that the tumor-starving drug Endostatin might be a magic bullet against cancer. In an interim report based on its first human tests, Endostatin halted some cancers and partially shrank one tumor, but had no spectacular effects in the first 39 patients treated.

      On the other hand, the drug seems virtually free of side effects, a remarkable feat for any cancer treatment.

      The preliminary findings were reported in abstracts, or short summaries, that researchers submitted last June for a major meeting on cancer being held in Amsterdam this week.

      One abstract from Dana-Farber/Partners Cancer Care in Boston said that ``several patients'' had stable disease, meaning the tumors neither grew nor shrank. In one patient with advanced pancreatic cancer, a very stubborn form of cancer, the tumor shrank by less than 50 percent, said the abstract.

      EntreMed Inc., the Maryland biotech company developing the drug that was discovered in the Boston laboratory of Dr. Judah Folkman, called the reports ``old news.'' More recent and complete results are to be presented Thursday at the meeting, sponsored by U.S. and European cancer organizations.

      About 60 patients in all are being treated in the Phase I trials of Endostatin in three cities: Boston, Houston and Madison, Wis. The trials began last fall and early winter, so the June reports released Monday represent only about half the duration of the Phase 1, or safety, trial.

      EntreMed stock dropped more than 4 points, and an analyst who follows the company said investors'' high expectations had been somewhat shaken, even though it is far too early to predict Endostatin''s merits.

      ``With Endostatin, there''s always been this aura around it due to its potent anti-angiogenic effect in mice,'' said Alan Auerbach, an analyst with First Security Van Kasper in Los Angeles.

      Endostatin is one of several dozen drugs called angiogenesis inhibitors, which are aimed at destroying a tumor''s blood supply without attacking the cancer directly. Folkman, the Children''s Hospital researcher who forged the angiogenesis field, says that the drugs will work far differently from conventional drugs and that holding tumors in check with these nontoxic drugs may be as good as a cure.

      Drugs'' activity in Phase I trials often isn''t a good indication of their future worth. With angiogenesis inhibitors this may be even more true. Folkman points out that with similar, but weaker, drugs, it has often taken as much as a year to begin having a marked effect. This is all the more reason, say supporters of the new drugs, to try them in less-sick patients.

      High hopes for Endostatin were raised in 1997 when Folkman and his colleagues reported that the drug shrank huge tumors in mice with no apparent toxic effects. Endostatin is among the most potent angiogenesis inhibitors discovered so far; it is a protein that''s a fragment of collagen protein that forms connective tissue in the body.

      (The Boston Globe Web site is at http://www.boston.com/globe/)

     

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