Efficacy and safety of thalidomide in the treatment of multiple myeloma.

The therapeutic efficacy of thalidomide ñ a derivative of glutamic acid ñ has been studied in numerous trials on refractory/relapsed multiple myeloma (MM) patients (1, 2). They showed that single-agent thalidomide can induce a partial response in approximately 30% of patients with refractory myeloma. The combination of thalido-mide with dexamethasone is active in approximately 50% of patients with refractory myeloma (3). The therapeutic efficacy of thalidomide increases significantly when it is combined with cyclophosphamide (4) or melphalan (5, 6) and used in front-line treatment (7, 8). Thalidomide exerts its anti-myeloma effect through different mechanisms. It can directly inhibit the growth and survival of myeloma cells; and it also targets marrow stromal cells (9). The aim of this study was to assess thalidomide tratment efficacy and draw attention to severe, especially cardiac, complications and possibility of extramedullary myeloma development following this therapy (10). EXPERIMENTAL Six patients with newly diagnosed and 26 patients with relapsed or refractory MM who have failed at least one prior line of treatment, including 3 patients treated with high dose therapy and autol-ogous stem cell transplantation, were treated with thalidomide at the Department of Hematology of the Institute of Hematology and Transfusion Medicine in Warsaw. Patients characteristics are presented in Table 1. As monotherapy, thalidomide (Myrin, Talizer or THA Pharmion GmbH, UK) was administered at a dose of 100 mg/day to a maximum dose of 400 mg/day. In 7 patients dexamethasone 40 mg on days 1-4, in a 28-day cycle, was added to the thalidomide (TD). Nine patients has been treated with MPT reg-imen, repeated every 4 weeks, which consisted of oral administration of melphalan at 4 mg/m 2 on days 1-7, oral prednisone at a dose of 40 mg/m 2 on days 1-7 and thalidomide 100 mg per day, continuously. CTD regimen, which was applied in 6 newly diagnosed MM patients, consisted of i.v. administration of cyclophosphamide at 500 mg/m 2 on day 1, dex-amethasone 20 mg on days 1-4; 8-11, in a 28-day cycle, and thalidomide 100 mg/day, continuously. Responses to treatment were assessed according to IMWG criteria (11). For treatment efficacy evaluation there were taken into account only those patients who received thalidomide alone for at least three months or at least 3 cycles of combination therapy. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC, Version 2.0). All patients gave written informed consent before entering the study, which …