Thalidomide in relapsed/refractory multiple myeloma: pivotal trials conducted outside the United States.

Recently completed phase II trials and retrospective analyses conducted outside the United States, primarily in Europe and Australia, have confirmed results of landmark US trials that established the efficacy of thalidomide in multiple myeloma. These trials evaluated thalidomide alone or in combination in patients with heavily pretreated relapsed/ refractory multiple myeloma. Single-agent thalidomide induced objective responses in approximately one third of patients and prolonged survival by approximately 1 year. These trials also indicated a possible dose-response relationship of thalidomide and identified several poor prognostic factors, including advanced age, high lactose dehydrogenase level, low platelet count, and low hemoglobin level. The combination of thalidomide with dexamethasone increased overall response by approximately 20% and reduced the time to response compared with thalidomide alone. In addition, lower doses of thalidomide used in the combination may increase patient tolerability. Finally, thalidomide in combination with chemotherapy yields response rates of approximately 60%, with median survival times of approximately 18 months. Randomized trials are needed to confirm these results and further explore the role of thalidomide in these treatment settings.