Given to 202 patients with advanced multiple myeloma, the drug – formerly known as PS-341 – achieved reduction of the disease in 67 patients, or 35 percent of 193 patients, and these responses continued for an average of 12 months. Importantly, 19 of the 67 had a complete or near-complete response. Overall patients survived for an average of 16 months.
These data, published in the June 26 issue of the New England Journal of Medicine, led the Food and Drug Administration to grant expedited approval to Millennium Pharmaceuticals of Cambridge, Mass., to provide Velcade to patients whose disease has relapsed after two previous treatments and is resistant to the last treatment.
"Velcade represents a new paradigm in myeloma treatment, as it targets both the tumor cell and bone marrow microenvironment to overcome resistance to conventional therapies," said Kenneth D. Anderson, MD, director of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber and senior author of the report. "This study shows that Velcade can be effective even in patients with advanced myeloma. It offers great potential to improve patient outcome in this disease."
This year, approximately 14,600 new cases of multiple myeloma will be diagnosed in the United States and 10,800 people likely will die from the disease. In multiple myeloma, cancerous plasma cells form abnormal proteins and damage the bone marrow, bone, and other vital organs. Standard treatment with combination chemotherapy and stem-cell transplants achieves responses, but myeloma remains incurable.
This phase II multicenter collaborative study was conducted at Dana-Farber, Massachusetts General Hospital, and a number of other medical centers. The trial included patients who had suffered relapses despite previous chemotherapy treatment, and whose disease was continuing to progress. The mean age of the group was 60 years. Patients received Velcade by injection twice a week for two weeks, then had a week with no treatment, for up to eight cycles, or 24 weeks. Those patients who did not respond adequately also were treated with oral dexamethasone, a steroid, on the day of and the day after Velcade treatment.
"The study showed improvement in various measures of clinical benefit for those patients with response, including quality of life, transfusion requirements, levels of normal immunoglobulin, and renal function," said Dana-Farber's Paul Richardson, MD, the paper's first author. "There also were a few common side effects: nausea, disturbance in bowel habit, low platelet and white blood cell counts, fatigue, and numbness and tingling in the arms and legs, but they were manageable in most cases."
Velcade belongs to a class of new drugs, called proteasome inhibitors. Proteasomes function to regulate protein turnover in normal and cancer cells. Velcade disrupts circuits mediating tumor growth and survival. In laboratory studies, Teru Hideshima, MD, PhD, of Dana-Farber showed that Velcade targets both the myeloma cell and its bone marrow microenvironment to overcome resistance to conventional chemotherapy.
The next step is to test Velcade in patients earlier in their disease course, explained Anderson, who is also the Kraft Family Professor of Medicine at Harvard Medical School. "Ongoing and future studies will determine how best to combine Velcade with other conventional and novel drugs to improve patient outcome," he said.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Journal
New England Journal of Medicine