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 effect upon its association with other drugs with proven efficacy 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 effects were moderate (grade <or=2) with only two patients in whom treatment was withdrawn due to neuropathy and severe somnolence.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 >or=2 were noted. Other side effects included grade <or=2 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 >50% 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.
INTRODUCTION:Thalidomide has recently proven to be a useful drug for treatment of refractory and relapsed multiple myelomapatients, up to 35% of whom achieve remission. However, little is known about the potential additive or synergistic effect upon its association with other drugs with proven efficacy 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 effects were moderate (grade <or=2) 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 >or=2 were noted. Other side effects included grade <or=2 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 >50% 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.
Authors: Kathrin Niemöller; Christian Jakob; Ulrike Heider; Ivana Zavrski; Jan Eucker; Olaf Kaufmann; Kurt Possinger; Orhan Sezer Journal: J Cancer Res Clin Oncol Date: 2003-04-17 Impact factor: 4.553