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bortezomib neuropathy

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https://www.readbyqxmd.com/read/28801984/low-dose-bortezomib-and-dexamethasone-as-primary-therapy-in-elderly-patients-with-waldenstr%C3%B3-m-macroglobulinemia
#1
Ya-Ping Zhang, Xi Yang, Zeng-Hua Lin, Xin-Feng Wang, Xin Cao, Xue-Fen You, Hong-Ming Huang, Wen-Yu Shi, Hong Liu
OBJECTIVE: This retrospective study was designed to determine the efficacy and safety of low-dose bortezomib and dexamethasone (lBD) in elderly Chinese patients with Waldenstrӧm macroglobulinemia (WM). METHODS: Ten WM patients aged over 60 years received first-line treatment with lBD. RESULTS: The median age was 70 years (range, 61-77 years). The overall response rate was 80%, including 1 patient who achieved a complete response, 1 patient with very good partial response, and 6 patients with a partial response...
August 12, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28801967/retreatment-and-prolonged-therapy-with-subcutaneous-bortezomib-in-patients-with-relapsed-multiple-myeloma-a-randomized-controlled-phase-iii-study
#2
Evangelos Terpos, Marco Gobbi, Anna Potamianou, Marjolein Lahaye, Catherine Couturier, Michele Cavo
OBJECTIVES: This randomized, international, multicenter, open-label phase III study investigated the effects of experimental retreatment with subcutaneous bortezomib plus dexamethasone (VD) followed by prolonged bortezomib therapy vs. standard VD retreatment in patients with relapsed/refractory multiple myeloma. METHODS: Patients were randomized (2:1) to receive either experimental (n = 53) or standard (n = 27) retreatment, stratified by the number of prior therapy lines...
August 12, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28706008/efficacy-and-safety-of-bortezomib-maintenance-in-patients-with-newly-diagnosed-multiple-myeloma-a-meta-analysis
#3
Chun-Yan Sun, Jun-Ying Li, Zhang-Bo Chu, Lu Zhang, Lei Chen, Yu Hu
Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here, we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID), and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both progression-free survival (PFS) (hazard ratio (HR) 0...
August 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28699668/poems-syndrome-2017-update-on-diagnosis-risk-stratification-and-management
#4
REVIEW
Angela Dispenzieri
DISEASE OVERVIEW: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy...
August 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28684537/pomalidomide-bortezomib-and-dexamethasone-pvd-for-patients-with-relapsed-lenalidomide-refractory-multiple-myeloma
#5
Jonas Paludo, Joseph R Mikhael, Betsy R LaPlant, Alese E Halvorson, Shaji Kumar, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Angela Dispenzieri, John A Lust, Prashant Kapoor, Nelson Leung, Stephen J Russell, David Dingli, Ronald S Go, Yi Lin, Wilson I Gonsalves, Rafael Fonseca, P Leif Bergsagel, Vivek Roy, Taimur Sher, Asher A Chanan-Khan, Sikander Ailawadhi, A Keith Stewart, Craig B Reeder, Paul G Richardson, S Vincent Rajkumar, Martha Q Lacy
This phase I/II trial evaluated the maximum tolerated doses (MTD), safety and efficacy of pomalidomide, bortezomib and dexamethasone (PVD) combination in patients with relapsed, lenalidomide refractory, MM. In the phase I, dose level 1 consisted of pomalidomide 4mg PO days 1-21, bortezomib 1.0 mg/m(2) IV or SQ days 1,8,15,22 and dexamethasone 40mg PO days 1,8,15,22 given every 28 days. Bortezomib was increased to 1.3 mg/m(2) for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28667459/clinical-pharmacokinetics-and-pharmacodynamics-of-panobinostat
#6
REVIEW
Mathilde Van Veggel, Elsbeth Westerman, Paul Hamberg
Histone deacetylase (HDAC) inhibitors cause an increase in acetylation that leads to an increase in DNA transcription and accumulation of different proteins, reducing cell proliferation and inducing cell death. Panobinostat is a first-in-line HDAC inhibitor approved for treating multiple myeloma in combination with bortezomib and dexamethasone. It is a pan-deacetylase inhibitor and therefore inhibits not only HDAC but also other deacetylases. The main mechanism of action of panobinostat is to inhibit HDAC, which causes cell cycle arrest and apoptosis, leading to it being an antineoplastic drug...
June 30, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28663117/bortezomib-induces-neuropathic-pain-through-protein-kinase-c-mediated-activation-of-presynaptic-nmda-receptors-in-the-spinal-cord
#7
Jing-Dun Xie, Shao-Rui Chen, Hong Chen, Hui-Lin Pan
Chemotherapeutic drugs, including bortezomib, often cause painful peripheral neuropathy, which is a severe dose-limiting adverse effect experienced by many cancer patients. The glutamate N-methyl-d-aspartate receptors (NMDARs) at the spinal cord level are critically involved in the synaptic plasticity associated with neuropathic pain. In this study, we determined whether treatment with bortezomib, a proteasome inhibitor, affects the NMDAR activity of spinal dorsal horn neurons. Systemic treatment with bortezomib in rats did not significantly affect postsynaptic NMDAR currents elicited by puff application of NMDA directly to dorsal horn neurons...
September 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#8
Claudia Wing, Masaaki Komatsu, Shannon M Delaney, Matthew Krause, Heather E Wheeler, M Eileen Dolan
The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy...
July 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28642620/pomalidomide-bortezomib-and-low-dose-dexamethasone-in-lenalidomide-refractory-and-proteasome-inhibitor-exposed-myeloma
#9
P G Richardson, C C Hofmeister, N S Raje, D S Siegel, S Lonial, J Laubach, Y A Efebera, D H Vesole, A K Nooka, J Rosenblatt, D Doss, M H Zaki, A Bensmaine, J Herring, Y Li, L Watkins, M S Chen, K C Anderson
This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m(2) days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort...
June 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28641642/-clinical-efficacy-of-cellular-immuotherapy-combined-with-bortezomib-for-the-treatment-of-patients-with-multiple-myeloma
#10
Yi-Ming Wang, Hao Long, Dan Yang, Jiang-He Shao
OBJECTIVE: To study the clinical efficacy of cellular immunotherapy combined with bortezomib for treatment of patients with multiple myeloma. METHODS: A total of 76 patients with multiple myeloma in our hospital from October 2012 to October 2013 were selected and randomly divided into 2 groups: the patients in 1 group (38 cases) were treated with cellular immunotherapy combined with chemotherapy including bortezomib (combined therapy group), the patients in other group(38 cases) were treated with only chemotherapy including bortezomib(single chemotherapy as control group)...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28632471/lenalidomide-as-a-treatment-for-relapsed-al-amyloidosis-in-an-hiv-positive-patient
#11
Johanna Denman, Kaveh Manavi, Mark Cook
We present a case of an HIV-positive man with systemic immunoglobulin light chain (AL) amyloid with cardiac involvement. At relapse, he was treated with lenalidomide and dexamethasone having previously developed autonomic neuropathy with bortezomib-based chemotherapy. The patient achieved a serological complete response with symptomatic improvement. After 11 cycles, lenalidomide was discontinued due to extensive ischaemia of the gastrointestinal tract. The patient remains symptomatically stable with normal levels of serum-free light chains 11 months after the treatment was discontinued...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28612296/kinesin-5-blocker-monastrol-protects-against-bortezomib-induced-peripheral-neurotoxicity
#12
Ilja Bobylev, Dominik Peters, Maulik Vyas, Mohammed Barham, Ines Klein, Elke Pogge von Strandmann, Wolfram F Neiss, Helmar C Lehmann
Neurotoxicity is a relevant side effect of bortezomib treatment. Previous reports have shown that the development of peripheral neuropathy caused by anti-neoplastic agents may be a result of reduced axonal transport. Based on evidence from prior studies that the kinesin-5 inhibitor monastrol enhances axonal transport and improves neuronal regeneration, we focused on the neuroprotective role of monastrol during the chemotherapeutic treatment with bortezomib. Prolonged treatment of C57BL/6 mice with bortezomib induced a length-dependent small-fiber neuropathy with axonal atrophy and loss of sensory nerve fibers...
June 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#13
REVIEW
Sara Bringhen, Edwin De Wit, Meletios-Athanassios Dimopoulos
Numerous treatments are available for relapsed and/or refractory multiple myeloma (MM), with safety profiles varying across drug classes and across agents within the same class. Thus, it is important to understand the toxicities of each antimyeloma agent when making treatment decisions. Neutropenia is commonly associated with lenalidomide and pomalidomide, and may be common with histone deacetylase (HDAC) inhibitors, but is relatively unusual with thalidomide, bortezomib, and carfilzomib. Infection was common in trials of lenalidomide and pomalidomide, and upper respiratory tract infection and pneumonia have been seen with carfilzomib...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28591409/impact-of-concomitant-dexamethasone-dosing-schedule-on-bortezomib-induced-peripheral-neuropathy-in-multiple-myeloma
#14
Shaji K Kumar, Jacob P Laubach, Thomas J Giove, Maureen Quick, Rachel Neuwirth, Godwin Yung, S Vincent Rajkumar, Paul G Richardson
Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce BiPN incidence and/or severity. We retrospectively analysed PN rates from 32 studies (2697 patients with previously untreated multiple myeloma) incorporating bortezomib and differing dexamethasone schedules: partnered dosing (days of and after bortezomib), weekly dosing, and other dosing schedules (e...
June 7, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28468087/-efficacy-and-safety-of-ctd-and-pcd-regimens-in-treatment-of-patients-with-newly-diagnosed-multiple-myeloma
#15
Y Gu, Y H Yuan, Q L Shi, X Y Qu, J Xu, R Guo, J D Xu, J Y Li, L J Chen
Objective: To observe the efficacy and safety of CTD (cyclophosphamide, thalidomide, dexamethasone) and PCD (bortezomib, cyclophosphamide, dexamethasone) regimens in treatment of patients with newly diagnosed multiple myeloma (NDMM) . Methods: A retrospective analysis was carried out on 88 cases of NDMM patients admitted to our hospital from July 2013 to January 2016, including 49 cases in CTD group and 39 cases in PCD group. The outcomes of two different regimens were analyzed, including response, prognosis, and adverse events...
April 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28455546/safety-of-btz-retreatment-for-patients-with-low-grade-peripheral-neuropathy-during-the-initial-treatment
#16
Aleksandra P Vidisheva, James Wang, Tanya M Spektor, Jacob D Bitran, Jose Lutzky, Imad A Tabbara, Joseph Z Ye, Sikander Ailawadhi, Laura V Stampleman, Ronald G Steis, Mehdi M Moezi, Regina A Swift, Tina M Maluso, Kyle A Udd, Shahrooz Eshaghian, Youram Nassir, James R Berenson
OBJECTIVE: Neuropathy is an important complication that may limit treatment options for patients with multiple myeloma. Previous studies have focused on treatment efficacy and have shown that retreatment with bortezomib (BTZ) is an effective treatment option. The goal of this study was to focus on the clinical manifestations of peripheral neuropathy (PN) and to retrospectively compare the incidence and severity of PN between the initial BTZ regimen and upon retreatment. Furthermore, this study evaluated how certain factors affect BIPN, which will help determine what conditions should be considered prior to retreatment...
April 28, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28446298/-clinical-effects-of-different-chemotherapeutic-regimens-on-the-patients-with-multiple-myeloma
#17
Shu Wang, Hong-Mei Guan
OBJECTIVE: To explore the clinical effects of T-VD regimen (bortezomib+dexamethasone+thalidomid) and T-VAD regimen (vincristine+adriamycin+dexamethasone+thalidomide) on the patients with multiple myeloma(MM). METHODS: Thirty cases of MM treated by T-VD(T-VD group) and 30 cases of MM treated by T-VAD(T-VAD group) from April 2010 to April 2012 were included in this study. The clinical effects and long-term survival were compared betwwen these 2 groups. RESULTS: Both the CR and ORR in T-VD group were higher than those in T-VAD group(P<0...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446297/-prophylaxis-of-bortezomib-induced-peripheral-neuropathy-in-patients-with-multiple-myeloma-by-high-dose-intravenous-mecobalamin
#18
Li-Li Zhang, Yi-Hao Wang, Zong-Hong Shao, Jun Ma
OBJECTIVE: To evaluate the efficacy and safety of high-dose intravenous mecobalamin (HDIME) for the treatment of bortezomib-induced peripheral neuropathy(BIPN) in the patients with multiple myeloma (MM). METHODS: A total of 65 newly diagonsed patients with multiple myeloma receiving bortezomib in Tianjin Medical University General Hospital were enrolled in this single-centre randomized clinical trial from July 2012 to May 2016. Out of 65 patients 38 in control group received bortezomib-based chemotherapy and 27 patients in HDIME group received the additional high-dose intravenous mecobalamin...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28430745/bortezomib-pharmacokinetics-in-tumor-response-and-peripheral-neuropathy-in-multiple-myeloma-patients-receiving-bortezomib-containing-therapy
#19
Sung-Eun Lee, Kyungmee Choi, Seunghoon Han, Jongtae Lee, Taegon Hong, Gab-Jin Park, Dong-Seok Yim, Chang-Ki Min
The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan-prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time-concentration curve during 3 h postdose (AUC0-3) in each patient...
July 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28427509/efficacy-and-safety-of-bortezomib-thalidomide-and-lenalidomide-in-multiple-myeloma-an-overview-of-systematic-reviews-with-meta-analyses
#20
REVIEW
Patricia Melo Aguiar, Tácio de Mendonça Lima, Gisele Wally Braga Colleoni, Sílvia Storpirtis
This overview summarizes evidence for the efficacy and safety of bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma. We searched the Medline, Scopus, and LILACS databases through August 2016, including systematic reviews with meta-analyses of randomized controlled trials assessing the efficacy and/or safety of bortezomib, thalidomide, or lenalidomide in patients with multiple myeloma. Two authors performed study selection, data extraction, and quality assessment using AMSTAR and GRADE instruments...
May 2017: Critical Reviews in Oncology/hematology
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