Related Pages Search for Clinical Trials NCI's PDQ® registry of cancer clinical trials. Multiple Myeloma/Other Plasma Cell Neoplasms NCI's gateway for information about multiple myeloma and other plasma cell neoplasms. Highlights from ASCO 2006 A collection of links to material summarizing some of the important clinical trial results announced at the 2006 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

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

Summary

Cutting the daily dose of the drug thalidomide from 400 mg to 100 mg significantly reduced the drug’s potentially severe side effects in patients with multiple myeloma that had come back or stopped responding to treatment, and without a significant impact on survival.

Source

American Society of Oncology (ASCO) annual meeting, Atlanta, Georgia, June 4, 2006 (see the meeting abstract).

Background

The drug thalidomide, which became infamous in the 1960s because of its association with severe birth defects, has shown effectiveness as a treatment for multiple myeloma, a cancer that develops in the bone marrow (the spongy tissue inside large bones). In May 2006 the U.S. Food and Drug Administration approved thalidomide for use in combination with another drug, dexamethasone, to treat newly diagnosed multiple myeloma. The drug appears to affect the blood supply that fuels the growth of tumors and may fight cancer in other ways, as well.

Thalidomide has also shown activity against multiple myeloma that has come back or is no longer responding to other therapies. However, many patients discontinue treatment because of the drug’s side effects, which can include blood clots, constipation, tingling in the hands and feet, and drowsiness.

Researchers in France thought it was possible that giving patients a much lower dose of thalidomide would reduce the drug’s side effects without reducing its effectiveness. The current study was conducted to confirm whether or not this was the case.

The Study

Four hundred patients were enrolled in the study. All of them had multiple myeloma that was progressing after at least one course of previous chemotherapy. Forty-five percent had received two or more courses. About half had received stem cell transplants.

The study was designed to be a noninferiority trial. Unlike other trials, which can determine whether one treatment is superior to another, noninferiority trials can only show that one treatment is “not worse” than another by a specified margin. In the current study, the researchers’ goal was to find out whether the one-year survival rate was similar between patients on lower-dose versus higher-dose thalidomide.

Researchers randomly assigned the patients to receive either the standard dose of thalidomide, 400 mg per day, or a lower dose of 100 mg per day. Following standard practice, patients also received the steroid dexamethasone three months after starting thalidomide or at an earlier point, if their disease progressed. Those at high risk for blood clots took blood-thinning medications to prevent this side effect.

The lead author of the study was Ibrahim Yakoub-Agha, M.D., of Lille University Hospital in Lille, France.

Results

After a median of one year of follow-up, about 74 percent of patients treated with 400 mg of thalidomide were alive, compared with about 69 percent of those treated with 100 mg. However, statistically, this difference was too small to be meaningful, said Yakoub-Agha, the study’s lead author.

Because this study was a noninferiority trial, these findings mean that the lower dose of thalidomide was no worse than the higher dose in keeping patients alive for at least one year.

Importantly, patients taking the lower dose of thalidomide had significantly lower rates of most side effects: 28 percent suffered from constipation, compared with 40 percent in the higher-dose group; 20 percent suffered from tingling in the hands and feet, compared with 32 percent in the higher-dose group; and 13 percent suffered from drowsiness, compared with 33 percent in the higher-dose group.

About the same number of patients in both groups suffered from blood clots. Overall, fewer patients in this study than in previous thalidomide studies had blood clots. The most likely explanation for this is that the patients most at risk for this side effect were given blood-thinning medications, said Yakhoub-Agha.

Patients in the lower-dose group needed more frequent doses of dexamethasone than patients in the higher-dose group. However, this did not change the fact that at the one-year mark, both groups had similar rates of overall survival.

Comments

This study showed that giving patients one-quarter of the standard dose of thalidomide resulted in a “clinically insignificant” decrease in survival and was much easier for patients to tolerate, said Yakhoub-Agha. These findings may enable more patients with multiple myeloma to take thalidomide and to take it for longer periods of time, he concluded.

Michael Bishop, M.D., a multiple myeloma specialist with the National Cancer Institute’s Center for Cancer Research, emphasizes that these findings apply only to patients with disease that has progressed after initial treatment, not to newly diagnosed patients who may still require the higher-dose of thalidomide.

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