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Key Words

Multiple myeloma, thalidomide, dexamethasone. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ³.)

Summary

Patients with previously untreated multiple myeloma responded better to induction therapy with the drug dexamethasone when thalidomide was added to the mix, a new study has found. However, patients who received thalidomide had higher rates of serious side effects. The study could not determine whether the addition of thalidomide ultimately lengthened patients’ lives.

Source

Journal of Clinical Oncology, in print Jan. 20, 2006; online December 19, 2005 (see the journal abstract).
(J Clin Oncol. 2006 Jan 20;24(3):431-6. Epub 2005 Dec 19)

Background

Multiple myeloma occurs when a type of white blood cell called a plasma cell starts reproducing uncontrollably. The plasma cells crowd out healthy blood cells in the bone marrow (the spongy tissue inside large bones), causing pain and gradually destroying the bone.

It’s estimated that about 16,000 people developed multiple myeloma in the United States in 2005 and more than 11,000 died from the disease. Treatments for the disease are effective at first, but the long-term outlook is generally poor. About 29 percent of patients are alive five years after diagnosis.

Recent studies have suggested that stem cell transplantation can put some patients’ multiple myeloma into remission. The transplanted stem cells help the bone marrow produce healthy cells, but only after the cancer cells are killed or reduced through induction chemotherapy. The standard pretransplantation induction therapy has been a combination of three drugs: vincristine, doxorubicin, and dexamethasone (VAD).

Several clinical trials have shown that thalidomide helps some patients whose previously treated multiple myeloma has come back. Given either alone or in combination with the chemotherapy drug dexamethasone, thalidomide increased response rates in patients with relapsed multiple myeloma that was unresponsive to other treatments.

In three unrandomized phase II trials, patients newly diagnosed with multiple myeloma responded well to treatment with thalidomide plus dexamethasone.

The Study

In this randomized phase III trial, a total of 207 patients with newly diagnosed multiple myeloma were assigned at random to four months of induction therapy with either dexamethasone alone or dexamethasone plus thalidomide. All patients were slated to undergo a subsequent bone marrow transplant.

To determine patients’ response to the induction therapy, researchers measured the levels of tumor markers in their blood and urine and the proportion of plasma cells in their bone marrow. Patients were counted as responding to treatment if

• tumor markers in their blood and urine disappeared or declined by at least half.
• the proportion of plasma cells in their bone marrow was less than three percent.
• they developed no new tumors and no existing tumors grew larger.
• levels of calcium in their blood remained normal. (High blood calcium levels are a sign of bone loss caused by too many plasma cells in the bone marrow.)

The study was conducted by the Eastern Cooperative Oncology Group, one of nine research groups supported by the National Cancer Institute to conduct large, multicenter cancer trials. The principal investigator was S. Vincent Rajkumar, M.D., of the Mayo Clinic in Rochester, Minn.

Results

Sixty-three percent of patients treated with dexamethasone plus thalidomide responded to induction therapy, compared with 41 percent of patients treated with dexamethasone alone, a statistically significant result. Disease progressed in two percent of patients treated with the combination regimen, compared with five percent of those who received only dexamethasone.

Rates of severe adverse effects were higher among patients who received thalidomide. These patients were more likely to have blood clots, high blood sugar levels, low blood calcium levels, fatigue, confusion, and constipation, among other side effects.

Limitations

The study was designed to compare induction therapy regimens in patients going on to have a stem cell transplant. Because induction therapy is not intended as a potential cure, the current study could not determine whether patients treated with dexamethasone plus thalidomide lived any longer than those treated with dexamethasone alone.

Comments

The superior response rate seen in patients treated with dexamethasone plus thalidomide “must be balanced against the greater toxicity seen with the combination,” the study authors conclude. They recommend that patients starting treatment with dexamethasone plus thalidomide receive anti-blood-clotting medication as a preventive measure.

Still, the study’s findings “represent a major advance,” write Paul Richardson, M.D., and Kenneth Anderson, M.D., of the Dana Farber Cancer Institute in Boston, in an accompanying editorial.

Michael Bishop, M.D., of the National Cancer Institute’s Center for Cancer Research. agrees. The findings, he says, “represent a new standard [for induction therapy], replacing VAD.” However, he adds, the standard may change once again after the completion of other clinical trials that are testing a different, perhaps even more effective induction therapy consisting of dexamethasone and the drug bortezomib (Velcade®).

Glossary Terms

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.

Initial treatment used to reduce a cancer. Induction therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called first-line therapy, primary therapy, and primary treatment.

A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.

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 decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although cancer still may be in the body.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells.

A drug that is used to treat multiple myeloma in patients who have just been diagnosed, and a painful skin disease related to leprosy. It is also being studied in the treatment of other types of cancer. Thalidomide belongs to the family of drugs called angiogenesis inhibitors. Also called Thalomid.

A substance that may be found in tumor tissue or released from a tumor into the blood or other body fluids. A high level of a tumor marker may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (in ovarian cancer), CA 15-3 (in breast cancer), CEA (in ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (in prostate cancer).

A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.