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https://www.readbyqxmd.com/read/29656050/an-expanded-treatment-protocol-of-panobinostat-plus-bortezomib-and-dexamethasone-in-patients-with-previously-treated-myeloma
#1
Vincent L Hansen, Morton Coleman, Stephanie Elkins, Jeffrey P Letzer, Moshe Yair Levy, Lasika Seneviratne, Jessica Rine, Marina White, Emil T Kuriakose
BACKGROUND: Panobinostat was recently approved by the US Food and Drug Administration and European Commission in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received ≥ 2 regimens, including bortezomib and an immunomodulatory drug. The PANEX (panobinostat expansion) treatment protocol provided access to panobinostat and gathered additional safety data before commercial availability. PATIENTS AND METHODS: In treatment phase 1, patients received panobinostat 20 mg 3 times per week plus bortezomib 1...
March 14, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29650268/efficacy-and-toxicity-profile-of-carfilzomib-based-regimens-for-treatment-of-multiple-myeloma-a-systematic-review
#2
REVIEW
Adeela Mushtaq, Vikas Kapoor, Azka Latif, Ahmad Iftikhar, Umar Zahid, Ali McBride, Ivo Abraham, Irbaz Bin Riaz, Faiz Anwer
Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone...
May 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29625927/tolerance-kinetics-and-depth-of-response-for-subcutaneous-versus-intravenous-administration-of-bortezomib-combination-in-chinese-patients-with-newly-diagnosed-multiple-myeloma
#3
Yan Xu, Shuhui Deng, Xuehan Mao, Gang An, Zengjun Li, Yafei Wang, Mariateresa Fulciniti, Matthew Ho, Jianhong Lin, Weiwei Sui, Wei Liu, Dehui Zou, Shuhua Yi, Wenyang Huang, Hong Liu, Rui Lv, Jian Li, Tingyu Wang, Chenxing Du, Nikhil C Munshi, Lugui Qiu
BACKGROUND: Peripheral neuropathy (PN) is an important toxicity that limits the use of bortezomib (Btz). Attempts to reduce PN have included its subcutaneous (SC) administration. PATIENTS AND METHODS: We retrospectively analyzed 307 patients with newly diagnosed multiple myeloma from a single Chinese center, receiving Btz-based regimens administered either via SC injection (SC group, n = 167) or intravenous (IV) infusion (IV group, n = 140). The efficacy and safety of Btz administration via SC and IV were then compared...
March 15, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29622862/the-effect-and-safety-of-bortezomib-in-the-treatment-of-al-amyloidosis-a-systematic-review-and-meta-analysis
#4
Fengjuan Jiang, Jin Chen, Hui Liu, Lijuan Li, Wenli Lu, Rong Fu
Bortezomib began to be used in the treatment of light chain (AL) amyloidosis in recent years. We performed the first meta-analysis of randomized clinical trials and clinical controlled trials to evaluate the effect and safety of bortezomib treatment for AL amyloidosis. We conducted a search (until July 2016) in electronic databases (PubMed databases and the Cochrane Central Register of Controlled Trials bases from the year 2003). There were 205 records we searched and eight studies was included (n = 617 persons)...
April 2018: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29603798/the-start-of-a-new-wave-developments-in-proteasome-inhibition-in-multiple-myeloma
#5
REVIEW
Kwee Yong, Sebastian Gonzalez-McQuire, Zsolt Szabo, Paul Schoen, Roman Hajek
Multiple myeloma (MM) accounts for 10% of hematological cancers. Stem cell transplantation remains the cornerstone of first-line treatment for eligible patients but, historically, pharmaceutical treatment options for MM have been limited. The proteasome was identified as a target for MM therapy in the early 2000s and, in 2004, the boronic acid proteasome inhibitor bortezomib gained European approval. Bortezomib now plays a major role in MM treatment, but the duration of its use can be limited by toxicities such as peripheral neuropathy, and the development of resistance...
March 30, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29600238/efficacy-and-tolerability-of-bortezomib-and-dexamethasone-in-newly-diagnosed-multiple-myeloma
#6
Mir Sadaqat Hassan Zafar, Afaq Ahmed Khan, Shyam Aggarwal, Manorama Bhargava
Background: Outcome in multiple myeloma (MM) has improved substantially over recent years as a result of the availability of multiple novel agents with acceptable safety profile. Study Design: Prospective observational study at a tertiary care institute. Methods: Twenty-five newly diagnosed patients of MM were treated with bortezomib and dexamethasone induction with monitoring for response and safety, followed by peripheral blood autologous stem cell transplant (PBASCT) in eligible patients or maintenance...
January 2018: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/29594921/bortezomib-maintenance-therapy-in-transplant-ineligible-myeloma-patients-who-plateaued-after-bortezomib-based-induction-therapy-a-multicenter-phase-ii-clinical-trial
#7
Atsushi Isoda, Kayoko Murayama, Shigeki Ito, Yoichi Kohara, Masaki Iino, Yuri Miyazawa, Morio Matsumoto, Hiroshi Handa, Yosuke Imai, Takuro Ishiguro, Wataru Izumita, Kiyoshi Kitano, Yukio Hirabayashi, Hideyuki Nakazawa, Fumihiro Ishida, Toru Mitsumori, Keita Kirito, Takaaki Chou, Hirokazu Murakami
In the era of novel therapeutic agents for multiple myeloma (MM), both the significance of achieving the plateau phase and the efficacy of subsequent maintenance therapy remain unclear. In the present study, we evaluated the efficacy and safety of bortezomib maintenance therapy (biweekly for 1 year) in transplant-ineligible MM patients who plateaued after bortezomib-based induction therapy. Of 36 evaluable patients, the overall response rate during induction therapy was 61%, with a stringent complete response in 6%, a complete response in 6%, a very good partial response in 17%, and a partial response in 33%...
March 28, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29574618/safety-and-comfort-of-domestic-bortezomib-injection-in-real-life-experience
#8
Claudio Cerchione, Davide Nappi, Anna Emanuele Pareto, Maria Di Perna, Irene Zacheo, Marco Picardi, Fabrizio Pane, Lucio Catalano
Despite novel agents, multiple myeloma is still an incurable disease, especially for elderly and frail patients, who are difficult to manage for concomitant comorbidities as the therapeutic options are limited and the response to chemotherapy is often short. We report our evaluations upon safety and efficacy of domestic subcutaneous bortezomib in elderly and frail patients candidate to bortezomib-melphalan-prednisone (VMP) regimen. We confirmed that overall incidence of adverse events, including peripheral neuropathy, was low, and in no case required admission to emergency service, contributing to reduce the rate of therapy discontinuation...
March 24, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29478257/bortezomib-plus-dexamethasone-versus-thalidomide-plus-dexamethasone-for-relapsed-or-refractory-multiple-myeloma
#9
Shinsuke Iida, Masashi Wakabayashi, Kunihiro Tsukasaki, Kenichi Miyamoto, Dai Maruyama, Kazuhito Yamamoto, Yoshifusa Takatsuka, Shigeru Kusumoto, Junya Kuroda, Kiyoshi Ando, Yoshitaka Kikukawa, Yasufumi Masaki, Miki Kobayashi, Ichiro Hanamura, Hiroaki Asai, Hirokazu Nagai, Kazuyuki Shimada, Norifumi Tsukamoto, Yoshiko Inoue, Kensei Tobinai
A randomized phase II selection design study (JCOG0904) was conducted to evaluate the more promising regimen between bortezomib (Bor) plus dexamethasone (Dex: BD) and thalidomide (Thal) plus Dex (TD) in Bor and Thal-naïve patients with relapsed or refractory multiple myeloma (RRMM). Patients ≥ 20 and < 80 years old with a documented diagnosis of symptomatic multiple myeloma (MM) with ≥ 1 prior therapies were randomized to receive BD (Bor 1.3 mg/m2 ) or TD (Thal 200 mg/day). In both arms, 8 cycles of induction (3-week cycle) were followed by maintenance phase (5-week cycle) until disease progression, unacceptable toxicity or patient refusal...
February 25, 2018: Cancer Science
https://www.readbyqxmd.com/read/29344912/capillary-leak-syndrome-as-a-complication-of-antibody-mediated-rejection-treatment-a-case-report
#10
Juan C Ramirez-Sandoval, Ricardo Varela-Jimenez, Luis E Morales-Buenrostro
We report a case of capillary leak that developed during treatment of antibody-mediated rejection in a kidney transplant recipient. A 53-year-old female transplant recipient experienced an increase in serum creatinine from 1.1 to 1.8 mg/dL. Antibody-mediated rejection was diagnosed by graft biopsy. She was treated with five plasmapheresis sessions (on alternate days with albumin replacement), five doses of immunoglobulin (5 g/dose at 100 mg/kg), a single dose of rituximab (500 mg), and four doses of bortezomib on days 1, 4, 7, and 10 (1...
January 17, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29339053/upregulation-of-nlrp3-via-stat3-dependent-histone-acetylation-contributes-to-painful-neuropathy-induced-by-bortezomib
#11
Cui-Cui Liu, Zhu-Xi Huang, Xiao Li, Kai-Feng Shen, Meng Liu, Han-Dong Ouyang, Su-Bo Zhang, Yu-Ting Ruan, Xiao-Long Zhang, Shao-Ling Wu, Wen-Jun Xin, Chao Ma
Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bortezomib treatment, and intrathecal injection of recombinant adeno-associated virus vector encoding NLRP3 markedly decreased paw withdrawal threshold of naive rats...
April 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29320913/a-phase-2-study-of-rituximab-cyclophosphamide-bortezomib-and-dexamethasone-r-cybord-in-relapsed-low-grade-and-mantle-cell-lymphoma
#12
Mohamad Bassam Sonbol, Talal Hilal, Amylou C Dueck, Allison C Rosenthal, Christopher R Conley, Heidi E Kosiorek, Brenda F Ginos, Katherine M Gano, Craig S Nichols, Jose F Leis, Patrick B Johnston, Thomas M Habermann, Donald W Northfelt, Peter Leif Bergsagel, David J Inwards, Thomas E Witzig, Stephen M Ansell, Craig B Reeder
In this phase 2 trial, we sought to evaluate the efficacy and safety of rituximab, cyclophosphamide, bortezomib, and dexamethasone (R-CyBorD) in patients with low-grade NHL. The regimen included rituximab on day 1 with weekly cyclophosphamide, dexamethasone, and bortezomib 1.3 mg/m2 IV in a 28-day cycle. Twenty one patients were enrolled on the study. Median age was 69 years (range 51-80) and 17 (81%) patients had two or more prior treatments. Histologies included FL (n = 8), MCL (n = 8), and LPL/WM (n = 5)...
January 10, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29219049/role-of-mitochondrial-mechanism-in-chemotherapy-induced-peripheral-neuropathy
#13
Mohammad Waseem, Pooja Kaushik, Heena Tabassum, Suhel Parvez
BACKGROUND: Even though chemotherapeutic regimens show considerable importance, it may cause progressive, continuing and sometimes irreversible peripheral neuropathy. Chemotherapy induced peripheral neuropathy (CIPN) is comprised of sensory abnormalities that are most distressing issues. The mechanism associated with CIPN pathogenesis is not completely revealed and its 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...
2018: 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
#14
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
#15
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...
January 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29121279/clinical-and-preclinical-perspectives-on-chemotherapy-induced-peripheral-neuropathy-cipn-a-narrative-review
#16
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
#17
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
#18
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...
January 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29034435/advances-in-the-treatment-of-paraproteinemic-neuropathy
#19
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
#20
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
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