Paul Richardson

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..This study is registered at http://www.clinicaltrials.gov as #NCT00833833...

..EXPERT OPINION: DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD...

..Concomitant ESA use with VMP/MP in previously untreated MM patients did not adversely affect TTP or OS, or increase thromboembolic risk. However, RBC transfusion was associated with significantly shorter survival...

..Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions...

..This case further supports that combination treatment with lenalidomide and bortezomib is an effective therapy in the management of patients with relapsed and refractory MM...

..Clinical trials are confirming the remarkable activity and improved tolerability of some of the new agents identified through this paradigm, providing exciting evidence of translational success in MM...

..Clinical development is ongoing to investigate its activity as monotherapy and in combination regimens for the treatment of non-Hodgkin's lymphoma, solid tumors, and early presentations of myeloma...

..Lenalidomide is active and well tolerated in relapsed, refractory myeloma, with the 30-mg once-daily regimen providing the basis for future studies as monotherapy and with dexamethasone...

..This review summarizes the profile of lenalidomide and the current evidence for its efficacy in multiple myeloma...

..This review presents recent data from clinical trials of these combinations and discusses their implications...

..Encouraging activity has been demonstrated with bortezomib in the first-line treatment of myeloma and in patients with mantle cell lymphoma. Investigations of its utility in the treatment of patients with solid tumors are ongoing...

..This review focuses on results from key phase II and III trials of bortezomib, thalidomide, and lenalidomide alone or in combination, and their emerging role in improving outcomes...

..The novel proteasome inhibitor bortezomib has shown antitumor activity in preclinical studies and has entered clinical trials, with encouraging results to date...

..This review therefore focuses on the extensive clinical data available from studies of these drugs in the treatment of newly diagnosed and advanced multiple myeloma...

..Its use in earlier-stage MM, other haematological malignancies and in solid tumours as monotherapy and in combination therapy is currently under investigation...

..Bortezomib, a first-in-class proteasome inhibitor, has shown clinical activity in relapsed, refractory multiple myeloma in a pivotal Phase II trial, SUMMIT...

..This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies...

..Chromosome 13 deletion and elevated beta2-microglobulin, generally considered poor prognostic factors, were not predictive of poor outcome with bortezomib in this study...

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..The use of bortezomib in MM therapy, including ongoing randomized phase III trials, is reviewed herein...

..Bortezomib was recently approved for the treatment of multiple myeloma. It is currently being investigated, both as a single agent and in combination, in phase I and II trials in a variety of tumor types...

..Lenalidomide is currently being tested in combination with both standard and novel agents, including bortezomib, for patients with relapsed/refractory multiple myeloma...

..Clinical development is ongoing to investigate its activity as monotherapy and in combination regimens for the treatment of non-Hodgkin's lymphoma, solid tumors, and earlier presentations of myeloma...

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..Available data suggest that bortezomib will be useful in the treatment of a variety of hematologic malignancies...

..These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy...

..Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity...

..In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD...

..Certain features associated with successful outcome may correlate with DF-related treatment effects, and prospective evaluation of DF therapy for severe VOD should allow better definition of predictors of response or failure...

..Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma. This study is registered at http://clinicaltrials.gov as NCT00378105...

..Additional clinical challenges discussed in this article are renal dysfunction, extramedullary disease, and advanced bone disease. Finally, participation in clinical trials is especially encouraged in this patient population...

..The study was closed prematurely for resource-based reasons, precluding dose comparison. Nonetheless, antitumour activity was observed, with promising response rates and promising severity of peripheral neuropathy...

..In addition, DF may be effective prophylaxis for VOD in high-risk patients. This review will focus on a summary of the pharmacology of DF and the clinical evidence for its use in VOD...

..The results of this study support additional studies of this combination approach in MM...

..Clinical data suggest that perifosine in combination with dexamethasone has activity in relapsed or relapsed/refractory MM...

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..Activity has also been demonstrated in chronic graft-versus-host disease and in symptom relief as part of palliative care...

..Regular screening and monitoring, combined with patient education and effective management strategies, can reduce the risk of these treatment-related complications, as well as their consequences...

..The purpose of this review is to discuss the pathophysiology and clinical features of VOD, and the current status and future directions of research for both prevention and treatment...

..This phase I, dose-escalation study (ie, NCT00153933) evaluated safety and determined the maximum-tolerated dose (MTD) of lenalidomide plus bortezomib in patients with relapsed or with relapsed and refractory MM...

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..Both trials showed responses (including complete responses) with manageable toxicities, forming the basis for an ongoing phase III trial comparing response to bortezomib versus high-dose dexamethasone...

..Bortezomib-associated peripheral neuropathy is manageable and reversible in most patients with relapsed myeloma. Dose modification using a specific guideline improves peripheral neuropathy management without adversely affecting outcome...

..To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma...

..Bortezomib should be considered an appropriate treatment for elderly and high-risk patients with relapsed multiple myeloma...

..These data support treatment with single-agent lenalidomide, as well as its use in steroid-sparing combination approaches. The study is registered at http://www.clinicaltrials.gov as NCT00065351...

..Baseline myeloma-associated neuropathy seems more common than previously reported, and bortezomib-associated neuropathy, although a common toxicity, is reversible in most patients...

..These studies provide the rationale for clinical trials of As2O3, either alone or together with dexamethasone, to overcome classical drug resistance and improve outcome in patients with MM...

..Our study therefore validates targeting pDC-MM interactions as a therapeutic strategy to overcome drug resistance in MM...

..Taken together, these results show that AZD6244 targets both MM cells and OCs in the BM microenvironment, providing the preclinical framework for clinical trials to improve patient outcome in MM...

..Together, these preclinical studies suggest that combining bortezomib with PK may enhance its clinical efficacy, reduce attendant toxicity, and overcome conventional and bortezomib resistance in patients with relapsed refractory MM...

..Together, these findings provide the framework for clinical evaluation of CDDO-Im, either alone or in combination with bortezomib, to overcome drug resistance and improve patient outcome in MM...

..These studies may therefore allow improved therapeutic use of 2ME2, based upon targeting genes that regulate MM cell growth and survival...

..MLN8237 is currently in phase 1 and phase 2 clinical trials in patients with advanced malignancies, and our preclinical results suggest that MLN8237 may be a promising novel targeted therapy in MM...

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..These studies provide the framework for clinical evaluation of MLN120B, alone and in combined therapies, trials of these novel agents to improve patient outcome in multiple myeloma...

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..1S cells and patient MM cells. Taken together, these results provide the preclinical rationale for the evaluation of SGN-40 as a potential new therapy to improve patient outcome in MM...

..Our studies therefore show that PI3K/p110delta is a novel therapeutic target in MM and provide the basis for clinical evaluation of CAL-101 to improve patient outcome in MM...

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..Taken together, our study provides the preclinical rationale for clinical protocols evaluating bortezomib together with NPI-0052 to improve patient outcome in MM...

..These findings have clinical significance, because identification of downstream apoptotic signaling after topoisomerase I inhibition will both elucidate mechanisms of resistance and optimize future combination chemotherapy against MM...

..Finally, a study using NVP-LAQ824 in a preclinical murine myeloma model provides in vivo relevance to our in vitro studies. Taken together, these findings provide the framework for NVP-LAQ824 as a novel therapeutic in MM...

..These results provide the preclinical rationale for clinical trials of CHIR-12.12 to improve patient outcome in multiple myeloma...

..These studies defined the mechanisms whereby IMiDs trigger NK cell-mediated tumour-cell lysis, further supporting their therapeutic use in MM...

..Combining NPI-0052 and Bortezomib induces synergistic anti-MM activity. Our study therefore provides the rationale for clinical protocols evaluating NPI-0052, alone and together with Bortezomib, to improve patient outcome in MM...

..These studies may therefore allow improved therapeutic uses of Dex, based upon targeting genes that regulate MM cell growth and survival...

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..Our study therefore provides the basis for the evaluation of CC-5013, either alone or in combination, to treat patients with MM at earlier stages of disease...

..Furthermore, they provide the framework for clinical evaluation of novel MM therapies based upon targeting NF-kappaB...

..Inhibition of JNK activity abrogates PS-341-induced MM cell death. These studies identify molecular targets of PS-341 and provide the rationale for the development of second-generation, more targeted therapies...

..These results, therefore, show that azaspirane both induces MM cell apoptosis and inhibits cytokine secretion in the BM milieu, providing the framework for clinical trials to improve patient outcome in MM...

..These studies, therefore, provide the framework for clinical use of this agent in combination with conventional chemotherapy...

..This treatment framework promises to improve outcome not only for patients with multiple myeloma, but also with other haematological malignancies and solid tumours...

..These data provide both insight into the molecular mechanisms of antitumor activity of PS-341 and the rationale for future clinical trials of PS-341, in combination with conventional and novel therapies, to improve patient outcome in MM...

..Our results therefore support clinical evaluation of AS703026, alone or in combination with other anti-MM agents, to improve patient outcome...

..Moreover, IKKbeta inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-kappaB activity in MM cells...

..Our data therefore demonstrate for the first time that inhibiting LPAAT-beta induces cytotoxicity in MM cells in the bone marrow milieu, providing the framework for clinical trials of these novel agents in MM...

..Our studies therefore demonstrate that LPAAT-beta inhibitor CT-32615 triggers necrosis, even in PS-341-resistant DHL-4 cells, providing the framework for its evaluation to overcome clinical PS-341 resistance and improve patient outcome...

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..Moreover, they define the functional association of IGF-IR and beta1 integrin in mediating MM cell homing, providing the preclinical rationale for novel treatment strategies targeting IGF-I/IGF-IR in MM...

..These molecular studies provide a framework for rational design of the next generation of combination therapies for WM...

..These results suggest that FTY720 overcomes drug resistance in multiple myeloma cells and provide the rationale for its clinical evaluation to improve patient outcome in multiple myeloma...

..Our study therefore provides the rationale for clinical protocols evaluating LBW242, alone and together with other anti-MM agents, to improve patient outcome in MM...

..These studies, therefore, provide the framework for clinical evaluation of mTOR inhibitors combined with IMiDs to improve patient outcome in MM...

..Taken together, our results provide the preclinical rationale for clinical protocols of HNK to improve patient outcome in MM...

..We investigated the antitumor effect of murine/human chimeric CD138-specific monoclonal antibody nBT062 conjugated with highly cytotoxic maytansinoid derivatives against multiple myeloma (MM) cells in vitro and in vivo...

..Combinations with dexamethasone (Dex), doxorubicin (Doxo) and bortezomib showed no antagonism. Our study highlights the potential role of the tumour microenvironment in modulating the activity of this drug class...

..The demonstrated anti-MM activity of PTK787, coupled with its antiangiogenic effects, provides the framework for clinical trials of this agent to overcome drug resistance and improve outcome in MM...

..g., dexamethasone and doxorubicin) or novel (e.g., bortezomib) anti-MM agents showed lack of antagonism. These results indicate that BEZ235 merits clinical testing, alone and in combination with other agents, in MM...

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..These studies therefore identify p38 MAPK as a novel therapeutic target to overcome drug resistance and improve patient outcome in MM...

..They provide a framework for the use of 2ME2, either alone or in combination with Dex, to overcome drug resistance and to improve outcome in MM...

..We summarize some of the trials leading to their approval and the current evidence for their clinical use. A number of promising agents undergoing phase I/II trial evaluation are also discussed...

..These results show that bortezomib was associated with significantly better multidimensional HRQL compared with dexamethasone, consistent with the better clinical outcomes seen with bortezomib...

..These preclinical studies provide the framework for clinical trials of bortezomib with Perifosine to improve patient outcome in MM...

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..The cis-imidazoline nutlin-3 can disrupt the p53-Hdm2 interaction and activate p53, inducing apoptosis in vitro in many malignancies, including multiple myeloma (MM)...

..Abstract Not Provided ..