The combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is feasible and can be an option for relapsed/refractory multiple myeloma RamoÂn GarcõÂa-Sanz 1 , Maria Isabel GonzaÂlez-Fraile 1 , Magdalena Sierra 1 , Carlos LoÂpez 1 , Marcos GonzaÂlez 1 and JesuÂs Fernando San Miguel* ,1 1 Servicio de HematologõÂa, Hospital Universitario de Salamanca y Centro de Investigacio Ân del Ca Âncer de Salamanca, Spain Introduction: Thalidomide has recently proven to be a useful drug for treatment of refractory and relapsed multiple myeloma patients, up to 35% of whom achieve remission. However, little is known about the potential additive or synergistic eect upon its association with other drugs with proven ecacy in MM. Material and methods: The present pilot study was designed to evaluate the toxicity and response rate of the association of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) in 22 refractory or relapsed MM patients. The protocol scheduled the administration of thalidomide at escalating doses (200 to 800 mg/day), daily oral cyclophosphamide (CTX) (50 mg/day) and pulsed dexamethasone (40 mg/day, four days every three weeks). Results: Adverse eects were moderate (grade 42) with only two patients in whom treatment was withdrawn due to neuropathy and severe somnolence. Infections were recorded in six patients, four requiring hospitalization for intravenous antibiotic therapy. No cases of thrombocytopenia grade 52 were noted. Other side eects included grade 42 constipation (29%), somnolence (35%) or dizziness (12%). In addition, one case of meralgia paresthetica and one with a deep venous thrombosis were noted. Two cases displayed hyperglycemia and myopathy attributed to dexamethasone, which was solved upon changing to prednisone. With a median follow-up of 12 months, 17 patients were evaluable for response; 13 (77%) responded to the therapy, including nine cases (53%) with a 450% M-component reduction (two of them with a complete remission). Only two responders have already progressed, with a projected event free survival of 51% at 12 months. Seven patients have died due to disease progression (n=5), sudden death (n=1) and infection (n=1). Conclusion: This study shows that ThaCyDex is a feasible and promising therapeutic approach for patients with relapsed/refractory MM. The Hematology Journal (2002) 3, 43 ± 48. DOI: 10.1038/sj/thj/6200150 Keywords: multiple myeloma; thalidomide; cyclophosphamide; dexamethasone Introduction Multiple myeloma (MM) accounts for approximately 1% of all human cancers and 10% of all hematological malignancies. 1 The current therapeutic approaches, especially the use of high-dose therapies with auto- logous or allogeneic stem cell rescue, together with an eective supportive therapy, have led to an improve- ment in disease outcome. 2±4 However, the disease currently remains incurable and eventually all patients relapse. In addition, options for salvage therapy in this group of patients are very limited. 2,5 This has stimulated the search for new active drugs and therapeutic strategies. 6 ± 13 Thalidomide (N-phthaloylglutamimide) is a glutamic acid derivative that has demonstrated activity in a series of advanced relapsed/refractory MM patients, including patients relapsing after high-dose therapy. 14 A recent update of this series has con®rmed the initial results with a 37% response rate, 15 a ®gure similar to that obtained by several other groups. 16 ± 18 Since thalidomide is a non-cytostatic agent without bone marrow toxicity, it seems reasonable to use it in combination with other agents in an attempt to increase the response rate. Moreover, thalidomide has been reported to restore the sensitivity of myeloma cells to other drugs and to *Correspondence: JF San Miguel, Department of Hematology, University Hospital of Salamanca, Paseo de San Vicente, 58-182, Salamanca, 37007, Spain; Tel: +34 923 291384; Fax: +34 923 294624; E-mail: sanmigiz@usal.es Received 6 August 2001; accepted 26 October 2001 The Hematology Journal (2002) 3, 43 ± 48 ã 2002 The European Haematology Association All rights reserved 1466 ± 4680/02 $25.00 www.nature.com/thj