Article

Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma.

Department of Haematology, St. Bartholomew's Hospital, London, UK.
British Journal of Haematology (Impact Factor: 4.94). 01/2009; 144(6):887-94. DOI: 10.1111/j.1365-2141.2008.07572.x
Source: PubMed

ABSTRACT This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2.5-10.0 mg/m(2)) on day 2 of a 28-day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty-three patients were enrolled. The MTD was defined at melphalan 7.5 mg/m(2) and bortezomib 1.3 mg/m(2). The overall response rate (ORR) was 68% (23% complete or near-complete responses [CR/nCR]) whilst at the MTD (n = 33) the ORR was 76% (34% CR/nCR). After median follow-up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD (P < 0.05 vs. non-MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low-dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted.

0 Bookmarks
 · 
68 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances in the treatment of multiple myeloma have resulted in improved response rates and overall survival in patients with multiple myeloma. These advances are largely due to thalidomide-, lenalidomide-, and bortezomib-based combinations that have improved response rates, not only in patients with untreated disease, but also in those with relapsed and/or refractory myeloma, in some cases producing response rates up to 85%. Eventually, however, nearly all patients relapse, emphasizing a continuing role for the introduction of investigational agents that overcome drug resistance. This article will review the current role for thalidomide, lenalidomide, and bortezomib-based combinations, as well as some preliminary findings for promising investigational agents currently in clinical trials for patients with relapsed and/or refractory disease.
    Medical Oncology 03/2010; 27 Suppl 1:S25-42. · 2.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The significance of ezrin immunoexpression and prognosis for osteosarcoma is still controversial. The aim was to provide a meta-analysis for ezrin immunoexpression and prognostic features of osteosarcoma patients. A detailed search was made in MEDLINE, EMBASE and the Web of Knowledge for relevant original articles published in English; methodological quality of the included studies was also assessed. Two reviewers extracted data independently. Studies were pooled and summary hazard ratios (HRs) and odds ratio (ORs) with corresponding confidence intervals (CIs) were calculated. Final analysis of 318 patients from 5 eligible studies was performed. Combined HR of ezrin immunohistochemical staining suggested that positive immunoexpression had an unfavorable impact on osteosarcoma patients' overall survival (n = 223 in 4 studies; HR = 4.79; 95% CI: 1.50-15.30; P = 0.008) but not on event-free survival (n = 202 in 3 studies; HR = 1.59; 95% CI: 0.61-4.15; P = 0. 0.342). Combined OR of ezrin immunohistochemical staining indicated that positive immunoexpression was associated with recurrence (n = 134 in 2 studies; OR = 3.79; 95% CI: 1.49-9.64; P = 0.005) but not with serum ALP level (n = 160 in 2 studies; OR = 2.16; 95% CI: 0.09-52.50; P = 0.637) and histological response to neoadjuvant chemotherapy(n = 260 in 4 studies; OR = 0.87; 95% CI: 0.37-2.03; P = 0.740). The results of this meta-analysis suggest that ezrin positive immunoexpression confers a higher risk of recurrence and a worse survival in osteosarcoma patients. Large prospective studies are needed to provide solid data to investigate the precise prognostic significance of ezrin.
    PLoS ONE 01/2013; 8(6):e64513. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Multiple myeloma (MM) is a neoplastic disorder. It results from proliferation of clonal plasma cells in bone marrow with production of monoclonal proteins, which are detectable in serum or urine. MM is clinically characterized by destructive bone lesions, anemia, hypercalcemia and renal insufficiency. Its prognosis is severe, with a median survival after diagnosis of approximately 3 years due to frequent relapses. Treatments for patients with relapsed/refractory MM include hematopoietic cell transplantation, a rechallenge using a previous chemotherapy regimen or a trial of a new regimen. The introduction of new drugs such as thalidomide, lenalidomide and bortezomib has markedly improved MM outcomes. When relapse occurs, the clinician's challenge is to select the optimal treatment for each patient while balancing efficacy and toxicity. Patients with indolent relapse can be first treated with a 2-drug or a 3-drug combination. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Autologous stem cell transplantation should be considered as salvage therapy at first relapse for patients who have cryopreserved stem cells early in the disease course. The aim of this review is to provide an overview on the pharmacological and molecular action of treatments used for patients with relapsed/refractory multiple myeloma.
    Clinical Medicine Insights: Oncology 01/2013; 7:209-219.

Full-text (2 Sources)

View
0 Downloads
Available from
Oct 6, 2014