Search results for "bortezomib"
showing 10 items of 60 documents
Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study.
2018
© 2018 The Authors.
Molecular mechanisms of carfilzomib-induced cardiotoxicity in mice and the emerging cardioprotective role of metformin
2019
AbstractCarfilzomib (Cfz), an irreversible proteasome inhibitor licensed for relapsed/refractory myeloma, is associated with cardiotoxicity in humans. We sought to establish the optimal protocol of Cfz-induced cardiac dysfunction, to investigate the underlying molecular-signaling and, based on the findings, to evaluate the cardioprotective potency of metformin (Met). Mice were randomized into protocols 1 and 2 (control and Cfz for 1 and 2 consecutive days, respectively); protocols 3 and 4 (control and alternate doses of Cfz for 6 and 14 days, respectively); protocols 5A and 5B (control and Cfz, intermittent doses on days 0, 1 [5A] and 0, 1, 7, and 8 [5B] for 13 days); protocols 6A and 6B (p…
Inhibition of Proteasomal Glucocorticoid Receptor Degradation Restores Dexamethasone-Mediated Stabilization of the Blood–Brain Barrier After Traumati…
2013
To establish the molecular background for glucocorticoid insensitivity, that is, failure to reduce edema formation and to protect blood-brain barrier integrity after acute traumatic brain injury.Controlled animal study.University research laboratory.Male C57Bl/6N mice.Mechanical brain lesion by controlled cortical impact.Our study demonstrates that 1) proteasomal glucocorticoid receptor degradation is established in brain endothelial cells after traumatic brain injury as a form of posttranslational glucocorticoid receptor modification; 2) inhibition of the proteasomal degradation pathway with bortezomib (0.2 mg/kg) in combination with the glucocorticoid dexamethasone (10 mg/kg) by subcutane…
Matched-pairs analysis of outcomes with bortezomib, melphalan, and prednisone (VMP) treatment for previously untreated multiple myeloma (MM) using lo…
2015
(95% CI: 58-88%), respectively. A formal interim analysis of the Day 90 CR rate was conducted when 65 patients were evaluable, and at that time the Mel only arm was determined to be superior. The study was, therefore, stopped early by the Institutional DSMB. However, with a longer follow up Bu-Mel ultimately resulted in better PFS. Conclusions: Bu-Mel was associated with a significantly lower day 90 CR rate and a significantly higher rate of grade 3-4 non-hematologic toxicity, compared to Mel. However, after a median follow up of 15.7 months, PFS was significantly longer in the Bu-Mel arm. Figure 1 PFS from Day 90 by Treatment Arm
Velcade, Intravenous Cyclophosphamide and Dexamethasone (VCD) Induction for Previously Untreated Multiple Myeloma (German DSMM XIa Trial).
2009
Abstract 131 Introduction. Autologous stem cell transplantation (ASCT) after cytoreductive induction is considered standard of care for younger patients (pts) with multiple myeloma (MM). The previous standard of induction, the Vincristin-Adriamycin-Dexamethasone (VAD) combination, achieves inferior results compared with induction regimens which combine the proteasome inhibitor Velcade (V = Bortezomib) with Dexamethasone (D)(=VD) and a cytostatic drug such as Doxorubicin (PAD = VD plus Doxorubicin). Velcade-based induction therapy was shown to translate into better myeloma control after high dose melphalan and to lead to prolonged progression-free survival. In order to find a more efficaciou…
DARATUMUMAB, BORTEZOMIB AND DEXAMETHASONE (DVD) VS BORTEZOMIB AND DEXAMETHASONE (VD) IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM): EFFICACY AND …
2017
8036 Background: Daratumumab (D), a human, CD38-targeting mAb, is well tolerated and induces deep and durable responses in patients (pts) with RRMM. We provide an update of CASTOR (NCT02136134), a multicenter, phase 3, randomized study of DVd vs Vd in RRMM. Methods: All pts received ≥1 prior line of therapy (LOT) and were administered 8 cycles (Q3W) of Vd (1.3 mg/m2 SC bortezomib on days 1, 4, 8, and 11; 20 mg PO/IV dexamethasone on days 1-2, 4-5, 8-9, and 11-12) ± D (16 mg/kg IV once weekly in Cycles 1-3, every 3 weeks for Cycles 4-8, then every 4 weeks until progression). Bortezomib-refractory pts were ineligible. Minimal residual disease (MRD) was assessed upon suspected CR and at 6 and…
Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma
2021
PETHEMA/GEM Cooperative Group.
Health-related quality of life maintained over time in patients with relapsed or refractory multiple myeloma treated with daratumumab in combination …
2020
In the phase III CASTOR trial, daratumumab, bortezomib and dexamethasone (D-Vd) significantly extended progression-free survival compared with bortezomib and dexamethasone (Vd) alone in patients with relapsed/refractory multiple myeloma (RRMM). Here, we present patient-reported outcomes (PROs) from the CASTOR trial. PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system questionnaire. Treatment effects through Cycle 8 were measured by a repeated measures mixed-effects model. After Cycle 8, PROs were only collected for patients in the D-Vd group who con…
Treatment for patients with relapsed/refractory mantle cell lymphoma: European-based recommendations
2017
International audience; Patients with mantle cell lymphoma (MCL) usually respond to initial combination chemotherapy, but the disease inevitably relapses and often follows an aggressive course. Here, clinical study results published since 2008 for patients with relapsed/refractory MCL were reviewed to compare available evidence for treatment guidance. Most trials identified were non-randomized, phase II studies performed at a limited number of sites, and many evaluated MCL as one of multiple non-Hodgkin lymphoma subtypes. Additional randomized, comparative trials are needed. Treatment selection generally depends on patient need, age and fitness, time of relapse, and line of therapy. Combina…
The proteasome inhibitor Bortezomib (Velcade) as potential inhibitor of estrogen receptor-positive breast cancer
2015
Around 70% of breast cancers express the estrogen receptor α (ERα) and depend on estrogen for growth, survival and disease progression. The presence of hormone sensitivity is usually associated with a favorable prognosis. Use of adjuvant anti-endocrine therapy has significantly decreased breast cancer mortality in patients with early-stage disease, and anti-endocrine therapy also plays a central role in the treatment of advanced stages. However a subset of hormone receptor-positive breast cancers do not benefit from anti-endocrine therapy, and nearly all hormone receptor-positive metastatic breast cancers ultimately develop resistance to anti-hormonal therapies. Despite new insights into me…