New cancer-fighting drug shows promise in study

An experimental drug that blocks a substance used by cancer cells to cheat death has showed promising early results in a handful of San Antonio cancer patients.

The drug, known as YM155, suppresses the production of the aptly named protein survivin, found in many types of tumors. Survivin not only prevents cancer cells from dying as they normally would, it also appears to make them resistant to traditional chemotherapy and radiation treatment.

“Our cells live in this beautiful harmony — much like the Earth — in which new cells are formed and an equal number of cells die off,” said Dr. Anthony Tolcher, director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio, who headed the study.

“But almost all solid-tumor malignancies have the presence of survivin. Survivin is a protein that shuts down normal cell death and thereby allows tumor cells to be immortal.”

Survivin has been an attractive target for cancer researchers because it's found in so many kinds of solid tumors. Researchers once thought that it was produced only in fetal cells and adult cancer cells. Recently, however, it has been found in several kinds of healthy adult cells.

YM155 is the first drug to block the production of survivin, although others are under development. In a Phase 1 study designed only to see if the drug is safe and well-tolerated, 41 patients — most from San Antonio — who had failed conventional treatment were given YM155. They included patients with non-Hodgkin's lymphoma, prostate cancer and colorectal cancer.

Although the study wasn't designed to gauge effectiveness — some patients only received low doses of the drug — three patients with B-cell lymphomas had impressive responses, including one whose cancer “melted away,” Tolcher said. Lesser responses were seen in two patients with prostate cancer and one with non–small-cell lung cancer.

Side effects included nausea, fever and mouth sores. One patient suffered kidney damage.

The results were published in today's Journal of Clinical Oncology. Tolcher is a paid adviser to the drug's manufacturer, Astellas Pharma, which funded the study.

In an accompanying editorial in the journal, Drs. Elisabeth G.E. de Vries and Steven de Jong of the University of Groningen, the Netherlands, said the drug's effectiveness “seems robust,” despite the limitations of the Phase 1 study, and that it might prove to be “an attractive drug to combine with other agents.”

Tolcher is launching a larger, Phase 2 study of the drug in B-cell lymphoma patients, and additional studies targeting other individual cancers are under way.

“I think this is a very promising drug in cancer — lymphomas, prostate cancer and the like,” he said.