Dexamethasone Improves Response to Thalidomide in Myeloma

Laurie Barclay, MD

January 10, 2003

Jan. 10, 2003 — Thalidomide plus dexamethasone may become the treatment of choice for myeloma patients with low tumor mass, according to the results of a study published in the Jan. 1 issue of the Journal of Clinical Oncology. Investigators found that this combination performed better than did thalidomide alone.

"Based on our prior experience in patients with resistant disease, we postulated that the combination of thalidomide-dexamethasone would induce rapid reduction of tumor mass, allowing prompt collection of autologous blood stem cells with granulocyte-colony-stimulating factor alone," write Donna Weber, MD, and colleagues from the University of Texas M.D. Anderson Cancer Center in Houston. "Although the mechanism of action of thalidomide remains unclear and may be related to antiangiogenic or direct antitumor effects against myeloma, the drug is effective despite resistance to multiple standard therapies."

In this study, 28 patients with previously untreated asymptomatic myeloma received thalidomide 100 to 200 mg orally at bedtime, with weekly increments of 50 to 100 mg as tolerated to a maximum of 600 mg at bedtime. Forty consecutive previously untreated patients with symptomatic myeloma received thalidomide according to the same regimen, except that maximum dose at bedtime was 400 mg, and they also received dexamethasone 20 mg/m 2 for four days beginning on days 1, 9, and 17, and the second and third cycles of repeated dexamethasone starting on day 30. Both groups of patients were treated for at least three months.

Patients treated with thalidomide-dexamethasone had a complete remission rate of 16% and a response rate of 72%, compared with a 36% response rate for patients treated with thalidomide alone. Median time to remission was 0.7 months with the combination and 4.2 months with thalidomide alone.

Five patients died: two as a direct result of multiple myeloma, one from infection, one from a possible thromboembolic event, and one from unknown causes. Grade 3 toxicity included infections in nine patients and thrombotic or embolic events in seven patients. The authors recommend further characterization of coagulation factors at baseline and during treatment and the preventive role of therapeutic anticoagulation in high-risk patients. Although most adverse events were mild and transient with dose reduction or temporary cessation of thalidomide, neuropathy was rarely irreversible.

"These uncommon side effects should not detract from the higher response rate of thalidomide-dexamethasone with little or no serious toxicity in the majority of patients," the authors write. "Among previously untreated patients with more advanced and symptomatic disease, the combination of thalidomide-dexamethasone doubled the response rate and induced remissions more rapidly, indicating that the combination of both drugs was superior to either alone.... Considering the ease of oral administration, the infrequency of serious irreversible side effects, and the rapidity of response permitting early stem cell collection, the combination of thalidomide-dexamethasone may well represent the treatment of choice for myeloma patients with disease of low or intermediate tumor mass."

J Clin Oncol. 2003;21:16-19

Reviewed by Gary D. Vogin, MD


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