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bortezomib neuropathy

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https://www.readbyqxmd.com/read/29219049/role-of-mitochondrial-mechanism-in-chemotherapy-induced-peripheral-neuropathy
#1
Mohammad Waseem, Pooja Kaushik, Heena Tabassum, Suhel Parvez
BACKGROUND: Even though chemotherapeutic regimens shows considerable importance, it may cause progressive, continuing and sometimes irreversible peripheral neuropathy. Chemotherapy induced peripheral neuropathy (CIPN) comprises of sensory abnormalities that are most distress issues. The mechanism associated with CIPN pathogenesis is not completely revealed and is treatment is still questionable. The purpose of this review was to investigate the role of mitochondria in CIPN. METHODS: This review is literature based that describes the mitochondrial mechanism underlying CIPN and the neuropathic complications associated with different antineoplastic agents...
December 7, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29208204/durable-renal-response-after-combination-of-bortezomib-corticosteroids-rituximab-and-plasmapheresis-for-late-antibody-mediated-renal-transplant-rejection%C3%A2
#2
Yanli Ding, Jean Francis, Amitabh Gautam, Linda Pelletier, Vaishali Sanchorawala, Karen Quillen
Late occurrence of antibody-mediated rejection (AMR), defined as occurring 6 months after transplantation, is associated with poor renal allograft survival, compared to early acute AMR and acute cellular rejection. The proteasome inhibitor bortezomib has multiple immunomodulatory effects on plasma cells, the source of donor-specific HLA antibodies which mediate AMR. MATERIALS AND METHODS: Consecutive patients who presented with biopsy-proven AMR and donor-specific anti-HLA antibodies (DSA) at a single institution between July 2011 and February 2015 were included...
December 6, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/29169873/modified-hypercvad-versus-bortezomib-hypercad-in-patients-with-relapsed-refractory-multiple-myeloma
#3
Megan M Saraceni, Emma Scott, Richard T Maziarz, Matthew B Siegel, Solange Bassale, Susie Jiing, Eva Medvedova
INTRODUCTION: Multiple myeloma (MM) is an incurable plasma cell malignancy, in which aggressive relapses might require salvage cytotoxic infusional chemotherapy. Several clinical trials that reported the efficacy of bortezomib led to institutional practice changes in which vincristine was replaced with bortezomib in the modified hyperCVAD regimen, creating a new treatment regimen, named "bortezomib-hyperCAD." PATIENTS AND METHODS: We retrospectively describe the effectiveness and tolerability of 2 chemotherapy regimens among 33 patients with relapsed and/or refractory MM...
November 2, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29121279/clinical-and-preclinical-perspectives-on-chemotherapy-induced-peripheral-neuropathy-cipn-a-narrative-review
#4
S J L Flatters, P M Dougherty, L A Colvin
This review provides an update on the current clinical and preclinical understanding of chemotherapy induced peripheral neuropathy (CIPN). The overview of the clinical syndrome includes a review of its assessment, diagnosis and treatment. CIPN is caused by several widely-used chemotherapeutics including paclitaxel, oxaliplatin, bortezomib. Severe CIPN may require dose reduction, or cessation, of chemotherapy, impacting on patient survival. While CIPN often resolves after chemotherapy, around 30% of patients will have persistent problems, impacting on function and quality of life...
October 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29094232/phase-i-trial-of-bortezomib-daily-dose-safety-pharmacokinetic-profile-biological-effects-and-early-clinical-evaluation-in-patients-with-advanced-solid-tumors
#5
Rastislav Bahleda, Marie-Cécile Le Deley, Apexa Bernard, Shalini Chaturvedi, Michael Hanley, Audrey Poterie, Anas Gazzah, Andreea Varga, Mehdi Touat, Eric Deutsch, Christophe Massard, Helgi Van De Velde, Antoine Hollebecque, Magali Sallansonnet-Froment, Damien Ricard, Hervé Taillia, Eric Angevin, Vincent Ribrag, Jean-Charles Soria
Purpose This phase I study investigated bortezomib in solid tumors used as a daily subcutaneous regimen. Previous regimens showed only modest activity in solid tumors which was potentially related to sub-optimal tumor penetration. We aimed at exploring if daily low dose administration of bortezomib may allow a greater and tolerable pharmacokinetic exposure which might be required for antitumor activity in solid tumors. Patients and methods This 3 + 3 design, dose escalation, monocentric study aimed at defining the maximum tolerated dose of daily low dose schedule of bortezomib...
November 2, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29056470/phase-2-open-label-study-of-bortezomib-cladribine-and-rituximab-in-advanced-newly-diagnosed-and-relapsed-refractory-mantle-cell-and-indolent-lymphomas
#6
Soham D Puvvada, José Guillen-Rodriguez, Abhijeet Kumar, Lora Inclán, Kara Heard, Xavier I Rivera, Faiz Anwer, Jonathan H Schatz, Daruka Mahadevan, Daniel O Persky
BACKGROUND: Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). PATIENTS AND METHODS: Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29034435/advances-in-the-treatment-of-paraproteinemic-neuropathy
#7
REVIEW
Eduardo Nobile-Orazio, Mariangela Bianco, Andrea Nozza
Purpose of review Several advances have been made on the pathogenesis and therapy of neuropathies associated with paraproteinemia (monoclonal gammopathy). It is important for the neurologist to understand the pathogenetic relevance of this association especially when the hematological disease does not require per se any therapy. Recent findings Treatment of the neuropathy in patients with malignant paraproteinemia is mainly addressed by the hematologist while the neurologist is mainly involved in the initial diagnosis and in deciding whether the neuropathy is caused by the disease or by the chemotherapy used for the disease...
October 16, 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29034113/low-neurotoxicity-of-onx-0914-supports-the-idea-of-specific-immunoproteasome-inhibition-as-a-side-effect-limiting-therapeutic-strategy
#8
Laura von Brzezinski, Paula Säring, Peter Landgraf, Clemens Cammann, Ulrike Seifert, Daniela C Dieterich
Application of the proteasome inhibitor Bortezomib for the treatment of haematopoietic malignancies such as multiple myeloma significantly improves the average overall survival of patients. However, one of the most severe side effects is the development of peripheral neuropathies caused by neurotoxic effects of Bortezomib limiting its therapeutic efficacy. With ONX-0914 a specific inhibitor of the β5i (LMP7)-immunosubunit containing proteasomes was developed that targets exclusively the proteasome subtypes mainly expressed in immune cells including B lymphocytes as the origin of multiple myeloma...
September 2017: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/28972650/characterisation-of-a-rat-model-of-bortezomib-induced-painful-neuropathy
#9
Natalie A Duggett, Sarah J L Flatters
BACKGROUND: Bortezomib (Velcade®) is a breakthrough treatment for multiple myeloma, significantly improving patient survival. However, its use is limited by painful neuropathy often resulting in dose reduction/cessation of first-line treatment due to lack of treatment. The aim of this study was to characterise a clinically-relevant rat model of bortezomib-induced painful neuropathy, using established evoked measures and novel ethological techniques, to aid drug discovery. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were injected intraperitoneally (i...
October 3, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28911826/immunoproteasome-selective-and-non-selective-inhibitors-a-promising-approach-for-the-treatment-of-multiple-myeloma
#10
REVIEW
Roberta Ettari, Maria Zappalà, Silvana Grasso, Caterina Musolino, Vanessa Innao, Alessandro Allegra
The ubiquitin-proteasome system (UPS) is the major non-lysosomal proteolytic system for the degradation of abnormal or damaged proteins no longer required. The proteasome is involved in degradation of numerous proteins which regulate the cell cycle, indicating a role in controlling cell proliferation and maintaining cell survival. Defects in the UPS can lead to anarchic cell proliferation and to tumor development. For these reasons UPS inhibition has become a significant new strategy for drug development in cancer treatment...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28906482/real-life-experience-with-bortezomib-based-regimens-in-elderly-comorbid-patients-with-newly-diagnosed-multiple-myeloma-polish-retrospective-multicenter-analysis
#11
Iwona Hus, Adam Walter-Croneck, Anna Masternak, Artur Jurczyszyn, Lidia Usnarska-Zubkiewicz, Łukasz Bołkun, Agnieszka Druzd-Sitek, Marcin Rymko, Jadwiga Łętowska, Ewa Lech-Marańda, Marcin Pasiarski, Anna Dmoszyńska
INTRODUCTION    Bortezomib was the first proteasome inhibitor approved in multiple myeloma therapy, initially for resistant/relapsed disease. Currently, VMP (bortezomib, melphalan, prednisone) is one of standard regimens recommended in a first line therapy for patients with multiple myeloma ineligible for high-dose chemotherapy/ autotransplantation (HDT/autoSCT) basing on the results of phase 3 clinical trial by Miguel et al that demonstrated its superiority to MP protocol.  OBJECTIVES    Patients participating in clinical trials are highly selected populations, so observations from clinical practice might provide important information for medical practitioners...
September 14, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28905189/bortezomib-and-low-dose-dexamethasone-with-or-without-continuous-low-dose-oral-cyclophosphamide-for-primary-refractory-or-relapsed-multiple-myeloma-a-randomized-phase-iii-study
#12
RANDOMIZED CONTROLLED TRIAL
Martin Kropff, Martin Vogel, Guido Bisping, Rudolf Schlag, Rudolf Weide, Wolfgang Knauf, Heinrich Fiechtner, Georgi Kojouharoff, Stephan Kremers, Wolfgang E Berdel
This phase III, open-label, randomized, controlled study aimed to evaluate the benefit of adding continuous low-dose oral cyclophosphamide to bortezomib-dexamethasone in patients with primary relapsed/refractory multiple myeloma. Patients were randomized 1:1 to receive up to eight 3-week cycles of bortezomib (1.3 mg/m(2)) and dexamethasone (20 mg; VD; n = 48) or bortezomib-dexamethasone plus oral cyclophosphamide (50 mg; VCD; n = 48). Median time to progression (primary endpoint) was slightly longer in the VD versus VCD group (12...
November 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28904172/fda-approval-summary-daratumumab-for-treatment-of-multiple-myeloma-after-one-prior-therapy
#13
Vishal Bhatnagar, Nicole J Gormley, Lola Luo, Yuan Li Shen, Rajeshwari Sridhara, Sriram Subramaniam, Guoxiang Shen, Lian Ma, Stacy Shord, Kirsten B Goldberg, Ann T Farrell, Amy E McKee, Richard Pazdur
On November 21, 2016, the U.S. Food and Drug Administration granted regular approval to daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on two randomized, open-label trials in which daratumumab was added to these backbone therapies. The MMY3003 trial demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone...
November 2017: Oncologist
https://www.readbyqxmd.com/read/28862883/randomized-phase-ii-study-of-r-chop-with-or-without-bortezomib-in-previously-untreated-patients-with-non-germinal-center-b-cell-like-diffuse-large-b-cell-lymphoma
#14
RANDOMIZED CONTROLLED TRIAL
John P Leonard, Kathryn S Kolibaba, James A Reeves, Anil Tulpule, Ian W Flinn, Tatjana Kolevska, Robert Robles, Christopher R Flowers, Robert Collins, Nicholas J DiBella, Steven W Papish, Parameswaran Venugopal, Andrew Horodner, Amir Tabatabai, Julio Hajdenberg, Jaehong Park, Rachel Neuwirth, George Mulligan, Kaveri Suryanarayan, Dixie-Lee Esseltine, Sven de Vos
Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1...
November 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28843768/carfilzomib-or-bortezomib-in-relapsed-or-refractory-multiple-myeloma-endeavor-an-interim-overall-survival-analysis-of-an-open-label-randomised-phase-3-trial
#15
RANDOMIZED CONTROLLED TRIAL
Meletios A Dimopoulos, Hartmut Goldschmidt, Ruben Niesvizky, Douglas Joshua, Wee-Joo Chng, Albert Oriol, Robert Z Orlowski, Heinz Ludwig, Thierry Facon, Roman Hajek, Katja Weisel, Vania Hungria, Leonard Minuk, Shibao Feng, Anita Zahlten-Kumeli, Amy S Kimball, Philippe Moreau
BACKGROUND: The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to compare overall survival between the two treatment groups. METHODS: ENDEAVOR was a phase 3, open-label, randomised controlled trial in patients with relapsed or refractory multiple myeloma...
October 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28842138/evaluation-of-bortezomib-induced-neuropathy-using-total-neuropathy-score-reduced-and-clinical-versions-and-nci-ctcae-v4-0-in-newly-diagnosed-patients-with-multiple-myeloma-receiving-bortezomib-based-induction
#16
Arjun Lakshman, Manish Modi, Gaurav Prakash, Pankaj Malhotra, Alka Khadwal, Sanjay Jain, Savita Kumari, Neelam Varma, Subhash Varma
BACKGROUND: Bortezomib-induced peripheral neuropathy (BiPN) is a dose-limiting adverse effect of bortezomib-based therapy for multiple myeloma (MM). The reporting of BiPN is variable because of the use of different neuropathy scales. Most investigators use the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). PATIENTS AND METHODS: We prospectively evaluated the incidence of BiPN in treatment-naive patients with MM receiving weekly cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in 28-day cycles using 3 neuropathy scores: Total Neuropathy Score-reduced (TNSr) and -clinical (TNSc), and NCI CTCAE v4...
August 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28836002/severe-refractory-cidp-a-case-series-of-10-patients-treated-with-bortezomib
#17
Kalliopi Pitarokoili, Min-Suk Yoon, Ilka Kröger, Anke Reinacher-Schick, Ralf Gold, Christiane Schneider-Gold
Treatment options for patients with aggressive chronic inflammatory demyelinating neuropathy are limited and include the anti-CD20 antibody rituximab and the immunosuppressive regime cyclophosphamide. We aimed to investigate retrospectively the efficacy of bortezomib, a proteasome inhibitor tackling highly metabolically active cell types such as plasma cells, in a case series of 10 treatment refractory CIDP patients. All patients reported showed a deterioration of the clinical CIDP scores under first-line treatment or escalating treatment with cyclophosphamide or rituximab...
September 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28827818/depletion-of-nerve-growth-factor-in-chemotherapy-induced-peripheral-neuropathy-associated-with-hematologic-malignancies
#18
Jeonghwan Youk, Young-Sook Kim, Jung-Ah Lim, Dong-Yeop Shin, Youngil Koh, Soon-Tae Lee, Inho Kim
OBJECTIVE: To investigate whether the depletion of nerve growth factor (NGF) is associated with the development of chemotherapy-induced peripheral neuropathy (CIPN) in patients with hematologic malignancy. METHODS: We prospectively enrolled hematologic cancer patients who had a plan to receive bortezomib, thalidomide, or vincristine. Baseline NGF levels were measured within one week before the start date of chemotherapy. Follow-up NGF levels were measured after four months from the start date of chemotherapy or the date when CIPN was initially diagnosed...
2017: PloS One
https://www.readbyqxmd.com/read/28801984/low-dose-bortezomib-and-dexamethasone-as-primary-therapy-in-elderly-patients-with-waldenstr%C3%B3-m-macroglobulinemia
#19
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 patients with WM 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
#20
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
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