SAN FRANCISCO - Scientists said yesterday that angiostatin and endostatin, the anti-tumor drugs that caused a sensation three years ago after it was revealed that they drastically shrank tumors in mice, were free of serious side effects when tested against cancer in people.
But investigators presenting results of early human testing of the drugs, which are being developed by EntreMed Inc. of Rockville, also focused on tempering unreasonable expectations for them. Endostatin investigator Dr. Roy Herbst said the drugs - designed to work by cutting off the blood supply to tumors - will most likely be used in combination with traditional therapies such as radiation and chemotherapy or perhaps with other biologic drugs being developed.
The caution comes on the heels of early results in humans that do not meet the spectacular, and some say unfair, expectations occasioned by publicity of the results of the two drugs in mice. It also comes as companies such as EntreMed develop new drugs that, like angiostatin and endostatin, are designed to attack cancer by focusing on molecular targets - rather than by using broad therapies that poison healthy tissues along with cancerous ones.
"We are trying to make sense of a new kind of way to treat cancer," said Dr. Lee Rosen of the University of California, Los Angeles, speaking at a forum Friday here in advance of the American Society of Clinical Oncology's annual meeting, a scientific convention at which hundreds of therapies are being highlighted.
Among them is Gleevec, made by Novartis AG, which the Food and Drug Administration approved last week for patients with advanced stages of chronic myeloid leukemia for whom standard therapy has failed. Yesterday, scientists reported that the same drug had also shown remarkable results when used to treat patients with a rare form of gastrointestinal stromal cancer.
In one Phase II trial of Gleevec, which largely involved gastrointestinal cancer patients who hadn't responded to previous therapies, 68 of 139 patients showed evidence that their cancer had regressed while on the drug, and 54 didn't get any worse, scientists said yesterday.
Gleevec works by interfering with a particular enzyme that triggers tumor growth in certain cancers.
Other molecularly targeted drugs highlighted at the gathering include cancer vaccines - one of which uses genetically altered cells derived from a patient's own blood to stimulate the body to attack cancer - and inhibitors of abnormal blood vessel growth such as angiostatin and endostatin.
Expectations have been high for angiostatin and endostatin, even though the two drugs are in the earliest stage of human testing, one designed to determine whether a drug is safe to take - not necessarily whether it works. The trials involved patients who were extremely ill and had not responded to other therapies.
In the Phase I trial of angiostatin at Thomas Jefferson University Hospital in Philadelphia, three of 19 patients did not get worse for up to six months, investigator Eduardo DeMoraes said in his presentation. In the trial of endostatin at M.D. Anderson Cancer Center in Houston, two of 25 patients showed some regression in tumors, at least for a time, investigators reported.
The endostatin results largely repeated those presented at a scientific gathering in Amsterdam where interim results were presented. Still, endostatin was given star treatment at yesterday's ASCO gathering, with principal investigator Herbst describing the trial results at a news conference attended by international media and at a session in the morning before thousands of scientists.
Asked whether endostatin was perhaps being given such treatment only because of the stir it caused three years ago, Herbst noted that scans done during the clinical trials showed that blood flow decreased to certain patients' tumors. Although patients' tumors ultimately grew, Herbst said, the scans and other tests used during the trials gave him confidence in the future of the drug.
"I think this has been a very successful Phase I endeavor," he said. "If we hadn't done these biologic markers, we might be scratching our heads."
But, he said, "It makes me comfortable and confidant we have something here."
There is also evidence in animals that the drugs might be more effective if given continuously or subcutaneously, rather than in daily infusions, as they have been in early tests. EntreMed is testing subcutaneous injection of angiostatin in a clinical trial in the Netherlands. And Herbst said M.D. Anderson is preparing to launch a trial of endostatin in combination with another therapy.