The Curative Effect Observation Of Bortezomib Combination With Dexamethasone In 35 Patients With Multiple Myeloma

Background Multiple myeloma ( MM ) is a disease that is clonal proliferation of plasma cells, 10% incidence rate in all hematological malignant tumor. Up to now, it still equals to an uncurable disease. It is characterized by the proliferation and accumulation of malignant plasma cells predominantly in the bone marrow, secretion of a monoclonal protein and normal immunoglobulins secretion inhibited resulting in widespread destructive bone lesions, clinically major symptoms contain ostealgia, anemia, hypercalcinemia, infection, renal insufficiency and so on. The efficacy of traditional chemotherapy is poor, complete remission less than 10%, the median survival time was only 3 years. Many times of chemotherapy lead to cross-resistance easily, and become a relapse/refractory MM. Traditional chemotherapy for relapsed / refractory MM even more unsatisfactory efficacy, remission period short, and with the increase in the number of chemotherapy,the worse prognosis. Autologous stem cell transplantation and other new method after high-dose chemotherapy could improve the remission rate and survival time of these patients. The median disease-free survival and overall survival time was 39.0 months and 64.6 months. But it will eventually relapsed and become incurable. Bortezomib, a new antineoplastic drug that is a proteasome inhibitor , it's ubiquitin– proteasomepathway has become the new target of treating multiple myeloma. It is confirmed that bortezomib, is active in the treatment of multiple myeloma, and it achieved encouraging response rate in relapsed or refractory multiple myeloma. According to the latest clinical trial results, combined with dexamethasone could enhance the therapeutic effect. The common complications of Bortezomib are weakness, thrombocytopenia, diarrhea, and peripheral neuropathy, et al. It is a safe and effective antitumor medicine.Objective To investigate the efficacy and toxicity of bortezomib in combination with dexamethasone for the treatment of patients with Multiple Myeloma, and search the clinical and theoretical basis for the new treatment of MM.Method Thirty newly diagnosed patients with multiple myeloma ( male 19, female 16 ),whose median age was 56 years old( range 35 - 80 years old ),were treated with bortezomib plus dexmethasone, in The Jilin University Sino-Japan Union Hospital during the year of 2006 - 2008. Patients were treated with bortezomib 1.0 - 1.3 mg·m-2 by intravenous bolus within 3～5s on days 1,4,8 and 11, followed by an intravenous injection of dexamethasone 20 - 40 mg·d-1 on the same day or on days 1 - 4 of a 3-week cycle .The combination with Thalidomide was used in 10 of patients .The patients had received one to eight cycles at least.Response to bortezomib was evaluated according to the criteria of the European Group for Blood and Marrow Transp lantation ( EBMT ) before initiation of each bortezomib chemotherapy course. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.Results During the follow-up with a median of 11( 1一33 )months, 26( 88.6% )patients responded to the treatment.10 Patients were complete remission( CR ),5 were near CR( nCR ),11 were Partial remission(PR),5 minor remission( MR ),2 were no remission( NR ) ,2 were Progressive disease ( PD ).The overall remission rate reaehed to 74.3%.The adverse events were thrombocytopenia( 20 patients, 57.1% ), fatigue( 6 patients, 17.1% ),peripheral neuropathy( 12 patients, 34.3% ), gastrointestinal symptoms( 5 patients, 14.3% ),elevated transaminase( 8 patients, 22.9% ), orthostatic hypotension( 2 patients, 5.7% ),infection( 3 patients, 8.6% ).But all the adverse events could be relieved by symptomatic treatment or bortezomib reduction.Conclusion Bortezomib combined with dexamethasone shows obvious merits on newly-diagnosed and Relapsed/Refractory multiple myeloma, such as :1.Quickliy effect, the treatment efficacy could be seen after 1 - 2 course, and with the increase in treatment, the complete remission rate increased accordingly.2.Synergies, bortezomib used in combination with dexamethasone enhance the efficacy.3.Higher reaction rate and complete remission rate, longer relief persistence time.4.Higher security and well tolaterated, less adverse events. The occurrence of toxicity does not increase with the more course of treatment, and the related toxicity can be predicted, controlled and reversible.