Experimental drug targets environment of cancer cells

Most doctors used to think that the way to cure cancer was to attack it with every conceivable weapon. Now some are trying, instead, to disrupt the disease’s environment.

In a clinical trial completed earlier this year, a drug based on this approach helped prolong the lives of a majority of people with late-stage multiple myeloma, a deadly cancer that destroys bone tissue.

The drug, Velcade, is known as a proteasome inhibitor. It stops enzymes called proteasomes from clearing cells of protein debris. Scientists hope that by preventing the proteasomes from doing their job, the cancer cells will become so dysfunctional, they’ll shut down and die.

“This is the first proteasome inhibitor to make it to the clinic,” said Dr. Ken Anderson, a Harvard professor and lead investigator in a new Velcade study. “What’s exciting about it is it can induce the death of cells that are resistant to conventional therapy.”

Velcade, which is made by Millennium Pharmaceuticals Inc. in Cambridge, Mass., is thought to work by interrupting the attachment of myeloma to bone marrow and by stopping the production of factors that the myeloma cell needs to grow and spread.

Traditional cancer treatment focuses on the cancer cells and, though it often works, the chemotherapy can weaken healthy cells. This can cause side effects from vomiting and weight loss to anemia and bone marrow suppression. Sometimes, cancer cells become resistant to the drugs.

“In addition to targeting the tumor cell, [Velcade] focuses on the host-tumor interaction and the environment where the tumor cell lives,” Anderson said. “Focusing on these two aspects will open up a vast new field of therapy.”

Proteasome inhibitor therapies should not cause the same kind of systemwide havoc that chemotherapy causes. Interrupting a normal cell process, however, can cause side effects. In the earlier clinical trials, some patients experienced a drop in platelets, cells needed for blood clotting, and occasional neuropathy, which is nerve damage causing pain and numbness. But many of those patients had experienced the problems before taking Velcade, Anderson said.

Moreover, for reasons that are still unexplained, cancer cells seem much more sensitive to proteasome inhibitors than normal cells are, Anderson says.

The Food and Drug Administration views Velcade promising enough to grant it fast-track status, which means it could be moved to the marketplace faster than usual if ongoing studies show it benefits patients with few remaining treatment options. Researchers also are studying Velcade’s effect on solid tumors, such as breast, lung and prostate cancers.

Fighting multiple myeloma

Multiple myeloma is bone-marrow cancer. Each year, about 15,000 Americans are diagnosed with it and about 11,200 die. Only 14% of people with the disease survive longer than five years.

In a study of 78 people taking the experimental drug Velcade:

20% had a greater than 90% reduction in a marker that indicates the amount of cancer present.

27% had a disease reduction of between 25% and 90%.

77% experienced tumor reduction or a stabilization of their disease.

A larger study of Velcade is underway at 66 sites. The study will compare the progress of 300 patients on Velcade with 300 patients on dexamethasone, a standard therapy. Results of that study are expected in 2004.