Progress Reports From The War On Cancer

Some 20,000 cancer specialists gathered in Atlanta in mid-May for the American Society of Clinical Oncology's annual meeting. There was much good news, although progress is coming very, very slowly. Here are some of the successes:


There is a problem with chemotherapy. It indiscriminately floods the body with poison, killing healthy cells along with cancerous ones. That means some of the most potent chemicals can only be used sparingly, if at all. Wyeth-Ayerst Research Div. has come up with a way of more precisely targeting chemotherapy: piggybacking a poison called calicheamicin onto a so-called monoclonal antibody.

The lab-created antibody targets a marker that is found only on acute myelogenous leukemia cells, a virulent and often fatal form of blood cancer. The antibody seeks out the marker, attaches to it, and injects its toxic payload into the cell. The result: Only the leukemia cells are poisoned.

The new drug, dubbed CMA-676, has been tested on 59 patients at 13 medical centers, and 21 have experienced remission. That rate is comparable with standard chemotherapy, but the patients weren't plagued by nausea, says Dr. Eric L. Sievers, the physician from the Fred Hutchinson Cancer Research Center who directed the trials. "This represents a whole new realm of cancer treatment," says Sievers. "Eventually, we may be able to administer very toxic compounds at the very beginnings of cancer," making it much more likely that all of the tumor cells are killed.


A major breakthrough in the treatment of breast cancer came last year, when the Food & Drug Administration approved Herceptin. This man-made antibody from Genentech Inc. targets a protein produced by the Her2 gene that's associated with particularly aggressive breast cancers. But that same protein can also appear in abnormal quantities in men with prostate cancer, such as New York Yankees manager Joe Torre. So researchers are now testing a Herceptin-like drug on men.

A team headed by Dr. Nicholas James of the University of Birmingham in England administered a two-drug regime--a Her2 antibody from Medarex Inc. in Annandale, N.J., combined with a growth factor that promotes the production of immune system cells. James believes the antibody will attach to Her2-positive cancer cells, and then the stimulated immune-system cells will kill the malignancies. Although James has conducted only one early-stage trial, 70% of 111 patients with untreatable prostate cancer showed positive results.


The final goal in cancer research is a treatment that will stop tumor growth without the harmful effects of chemotherapy, radiation, or even surgery. With this aim, two of the hottest areas of cancer research are anti-angiogenesis and immunotherapy. The former seeks to starve a tumor by cutting off the growth of blood vessels that bring it nourishment, while the latter stimulates the body's own immune system to attack the tumor.

Now, there's a promising drug that does both. Discovered in Russia and licensed to Cytran Inc. in Kirkland, Wash., IM862 is delivered via an unusually easy method--nose drops. Because it's a very small molecule, it easily passes through the mucous membranes in the nostrils. In the blood stream, it boosts the production of interleukin-12, enhancing the immune system, and curbs the production of VEGF, which stimulates blood-vessel growth.

In an early-stage clinical trial, a research team led by Dr. Parkash Gill, professor of medicine at the University of Southern California, tested the drug on 44 patients with advanced Kaposi's sarcoma. This AIDS-related skin cancer currently can be treated only by highly toxic chemotherapy that can't be taken for very long. Gill reports that the nose drops produced total or major remissions in more than one-third of the patients, with minimal side effects. A larger, final-phase trial is under way, and Gill says there's no biological reason the drug could not work against other cancers as well.


Although everyone would like to increase survival rates for cancer, patients are almost as concerned about the quality of their life as its length. So drug companies and researchers are constantly searching for ways to make treatments easier to take or tolerate, even if survival rates stay the same.

An example is Bristol-Myers Squibb Co.'s Orzel, the first oral treatment for colon cancer. The experimental drug combines two chemotherapy agents, leucovorin and a new version of fluorouracil (5-FU), in pill form. In two large-scale studies of more than 1,100 patients in the U.S., Canada, and Europe, researchers report that Orzel was no less effective than standard colon cancer chemotherapy--a similar combination of fluorouracil and leucovorin but given intravenously. The pill was equally effective in terms of tumor shrinkage and survival rates. But patients exhibited far fewer side effects, such as nausea, and were able to self-administer the drug at home.

"A laudable goal of drug developers is to come up with alternative therapies that reduce toxicity," notes Dr. Richard Pazdur, professor of medicine at the University of Texas M.D. Anderson Cancer Center. Meanwhile, quality of life improvements cannot be dismissed.