The drug, a new type of treatment that targets a specific cell function in a way that kills cancer cells but leaves healthy cells untouched, extended the lives of very ill patients by an average of a year, says Dr. Paul Richardson, an oncologist from Dana-Farber Center Institute in Boston. The institute headed the multi-center study of 200 people with advanced cases of multiple myeloma.
The FDA accepted the results of this study, a Phase II trial, as a priority review in January. That means the agency will decide whether to approve the drug, called bortezomib (brand name Velcade), within six months of the acceptance date, rather than the normal 10 months. The FDA has a priority review designation for drugs that, if approved, would be a significant improvement compared to current products.
"These patients were extremely ill and had been through at least six therapies. The way these therapies work is that as the disease progresses, each new therapy usually works half as well as the one that came before," Richardson says, meaning that one therapy will hold the disease at bay for, say, six months, but the next one will help the patient for only three months.
"But with Velcade, the therapy improved the patients' symptoms for twice as long as the previous therapy," he says.
Moreover, the method by which the drug works shows great promise for treating other cancers, says a director of the company that makes the drug.
"This opens up a whole new pathway for treating cancer," says Dr. David Schenkein, director of clinical oncology for Millennium Pharmaceuticals, which sponsored the Dana-Farber clinical trials.
Velcade is a drug that inhibits a complex of enzymes called proteasomes, which can be instrumental in cell division, Schenkein says. When the proteasomes are inhibited, cell division can be compromised and cells can die. What researchers found is that cancer cells are particularly vulnerable to this proteasome inhibition.
"Many cancers are very dependent on proteins and the pathways that are regulated by proteasomes. What we found was that you can turn off the proteasome for a very short period of time, and while normal cells are able to handle that pause and resume their normal activity, cancer cells are so dependent on the proteins that if you can turn off the proteasome for a short period of time, it causes the death of the cancer cells," Schenkein says.
Beginning last June, Millennium began a larger, randomized trial of Velcade, which includes 600 patients at 66 hospital around the world whose multiple myeloma is not as advanced as those patients in the smaller trial. These patients have had a minimum of three treatments before taking Velcade. The study directly compares the outcomes of Velcade to standard treatments for multiple myeloma.
Dr. Gordan Srkalovic, a staff physician at the Taussig Cancer Center at the Cleveland Clinic, treated approximately a dozen bone cancer patients with Velcade as part of the Phase II study, which determines the drug's safety and effectiveness. He says the Phase III randomized trial will better prove if Velcade is superior to other treatments in ensuring longer-lasting, disease-free survival because the effects of one treatment are compared directly to the results of another treatment in the same study.
"In the Phase II trial, you're comparing the results to historical controls rather than to the results of a randomized study," he says, "and while it looked like there was longer-lasting disease survival times than other treatments, we still don't have that information."
However, he adds, "what is extraordinary is the unique mode of action of the drug. It is different from any other agent used in oncology."
This means, he says, that it has great potential for therapeutic value in the future, as researchers continue to test it both by itself and in combinations with other drugs to treat cancer.
Multiple myeloma is a cancer of the plasma cells of the immune system, where abnormal plasma cells form tumors, especially in the bone marrow. Approximately 14,600 people will get multiple myeloma in 2003, and another 10,900 will die from the disease, according to the American Cancer Society.