Thalidomide and dexamethasone combination for refractory multiple myeloma

Background: Thalidomide is effective in approximately 30% of patients with refractory multiple myeloma. Dexamethasone is active in 25% of patients wit h disease resistant to alkylating agents. We investigated the combination o f thalidomide with dexamethasone as salvage treatment for heavily pretreate d patients with multiple myeloma, in order to assess its efficacy and toxic ity. Patients and methods: Forty-four patients with refractory myeloma were trea ted with thalidomide, 200 mg p.o. daily at bedtime, with dose escalation to 400 mg after 14 days, and dexamethasone, which was administered intermitte ntly at a dose of 20 mg/m(2) p.o. daily for four days on day 1-4, 9-12, 17- 20, followed by monthly dexamethasone for four days. Patients' median age w as 67 years. All patients were resistant to standard chemotherapy, 77% were resistant to dexamethasone-based regimens and 32% had previously received high-dose therapy. Results: On an intention-to-treat basis twenty-four patients (55%) achieved a partial response with a median time to response of 1.3 months. The thali domide and dexamethasone combination was equally effective in patients with or without prior resistance to dexamethasone-based regimens and in patient s with or without prior high-dose therapy. Toxicities were mild or moderate and consisted primarily of constipation, morning somnolence, tremor, xeros tomia and peripheral neuropathy. The median time to progression for respond ing patients is expected to exceed 10 months and the median survival for al l patients is 12.6 months. Conclusion: The combination of thalidomide with dexamethasone appears activ e in patients with refractory multiple myeloma. If this activity is confirm ed, further studies of this combination as second-line treatment for patien ts resistant to conventional chemotherapy, and as primary treatment for pat ients with active myeloma, should be considered.