Related Pages Search for Clinical Trials 1 NCI's PDQ® database of cancer clinical trials. Multiple Myeloma/Plasma Cell Neoplasms Home Page 2 NCI's gateway for information about multiple myeloma and other plasma cell neoplasms. Highlights from ASCO 2004 3 A collection of links to material summarizing some of the important clinical trial results announced at the 2004 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Multiple myeloma, bortezomib (Velcade®), dexamethasone . (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁴.)

Summary

Early results from an international phase III trial show that bortezomib (Velcade®), a new targeted cancer drug, is more effective than a standard therapy, the drug dexamethasone, at delaying disease progression in patients with multiple myeloma that has relapsed or become resistant to other treatments. In addition, after a median of eight months’ follow-up fewer patients taking bortezomib had died. These results were so encouraging that the trial was stopped early and patients who were taking dexamethasone were allowed to switch to bortezomib.

Source

American Society of Clinical Oncology (ASCO) annual meeting, New Orleans, June 5, 2004.

Background

Multiple myeloma is characterized by a proliferation of white blood cells called plasma cells. This abnormal flood of cells crowds out healthy blood cells in the bone marrow (the spongy tissue inside large bones) and can lead to fatigue, bone pain, anemia, kidney failure, and/or recurrent infections.

More than 14,000 cases of multiple myeloma are diagnosed each year in the United States. With standard treatments, about 29 percent of patients survive for five years. No single standard therapy currently exists for multiple myeloma that has relapsed or become resistant to treatment. Patients may be treated with multidrug chemotherapy or with high doses of the drug dexamethasone, a corticosteroid. Some patients may be candidates for high-dose chemotherapy combined with a bone marrow transplant.

In early-phase studies, bortezomib - the first drug in a new class of targeted cancer therapies - demonstrated effectiveness against resistant or relapsed multiple myeloma. Bortezomib works by blocking proteasomes, clusters of proteins necessary for cancer cell growth. The U.S. Food and Drug Administration granted bortezomib “fast track” approval in May 2003 for the treatment of patients with multiple myeloma whose disease has progressed after at least two courses of treatment.

The Study

Conducted at 94 centers in the United States, Canada, Europe, and Israel, the study enrolled 669 patients with relapsed or resistant multiple myeloma. All patients had already received between one and three courses of treatment. They were randomly assigned to receive either bortezomib or dexamethasone. This was the first large randomized controlled trial (considered the “gold standard” in cancer research) of bortezomib.

The primary aim of the study was to find out whether treatment with bortezomib would stop the disease from progressing for longer than treatment with dexamethasone. The study’s principal investigator was Paul G. Richardson of the Dana-Farber Cancer Institute in Boston.

Results

After a median follow-up period of eight months, patients treated with bortezomib lived for a median of 5.7 months before their disease progressed. By contrast, patients treated with dexamethasone lived for a median of 3.6 months before their disease progressed.

After one year, 89 percent of patients in the bortezomib group were still alive, compared with 65 percent of those in the dexamethasone group. To date, 48 patients taking bortezomib have died, compared with 81 patients taking dexamethasone. Serious infections were less frequent in patients treated with bortezomib.

Limitations

These results are preliminary, says Wyndham Wilson, M.D., Ph.D., of the National Cancer Institute’s Center for Cancer Research, and the added time before disease progression among patients taking bortezomib (two months) is modest. Longer follow-up is necessary, he says, before it will be clear that bortezomib sets a new standard of care for relapsed or resistant multiple myeloma.

However, because the trial was stopped early and patients on dexamethasone were permitted to switch to bortezomib, it will be difficult for this trial to definitively determine, even with longer follow-up, whether bortezomib extends patients’ long-term survival and, if it does, by how much.

Comment

“Bortezomib is a very promising new targeted agent,” says Wilson. “The fact that there were fewer deaths among patients in the bortezomib group strongly suggests that the drug does extend patients’ survival.”

Given these highly encouraging preliminary results, adds Wilson, it would have been unethical not to offer study participants taking dexamethasone the opportunity to switch to bortezomib.

Glossary Terms

A drug that is being studied in the treatment of cancer. It belongs to the family of drugs called dipeptidyl boronic acids. Also called PS-341.

A synthetic steroid (similar to steroid hormones produced naturally in the adrenal gland). Dexamethasone is used to treat leukemia and lymphoma and may be used to treat some of the problems caused by other cancers and their treatment.

A statistics term. The middle value in a set of measurements.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called standard of care or best practice.

A type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. A monoclonal antibody is a type of targeted therapy.