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bortezomib neuropathy

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https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#1
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...
June 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28642620/pomalidomide-bortezomib-and-low-dose-dexamethasone-in-lenalidomide-refractory-and-proteasome-inhibitor-exposed-myeloma
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28408615/phase-ii-study-of-bortezomib-in-combination-with-cyclophosphamide-and-rituximab-for-relapsed-or-refractory-mantle-cell-lymphoma
#14
Hun Ju Lee, Jorge E Romaguera, Lei Feng, Aakash P Desai, Liang Zhang, Michelle Fanale, Felipe Samaniego, Fredrick B Hagemeister, Luis E Fayad, Maria A Rodriguez, Jeffrey L Medeiros, Kimberly Hartig, Krystle Nomie, Makhdum Ahmed, Maria Badillo, Haige Ye, Yasuhiro Oki, Pei Lin, Loretta Nastoupil, Jason Westin, Michael Wang
BACKGROUND: Relapsed or refractory mantle cell lymphoma (MCL) has a poor prognosis. The best outcome is achieved in patients who have a partial or complete response to salvage treatment and proceed to allogeneic stem cell transplant. PATIENTS AND METHODS: Twenty-one patients were given a combination regimen of bortezomib, cyclophosphamide, and rituximab at MD Anderson Cancer Center as part of a single-arm, prospective, open-label phase II clinical trial. The median age was 66 years, with a median number of prior treatments of three...
May 2017: Oncologist
https://www.readbyqxmd.com/read/28401497/bortezomib-combined-with-standard-induction-chemotherapy-in-japanese-children-with-refractory-acute-lymphoblastic-leukemia
#15
Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Yukayo Terashita, Tadashi Ariga, Yosuke Hosoya, Shinsuke Hirabayashi, Atsushi Manabe, Keisuke Hara, Tetsuya Aiba, Tsugumi Shiokawa, Hiroko Tada, Norihiro Sato
Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study...
April 11, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28382618/effects-of-single-agent-bortezomib-as-post-transplant-consolidation-therapy-on-multiple-myeloma-related-bone-disease-a-randomized-phase-ii-study
#16
Orhan Sezer, Meral Beksac, Roman Hajek, Gülsan Sucak, Seckin Cagirgan, Werner Linkesch, Olga Meltem Akay, Zafer Gülbas, Hareth Nahi, Torben Plesner, John A Snowden, Ayşen Timurağaoğlu, Tobias Dechow, Alois Lang, Tülin Tuğlular, Johannes Drach, Gabriele Armbrecht, Anna Potamianou, Catherine Couturier, Robert A Olie, Caroline Feys, Nathalie Allietta, Evangelos Terpos
This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m(2) intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation)...
April 6, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28379796/lenalidomide-bortezomib-and-dexamethasone-with-transplantation-for-myeloma
#17
RANDOMIZED CONTROLLED TRIAL
Michel Attal, Valerie Lauwers-Cances, Cyrille Hulin, Xavier Leleu, Denis Caillot, Martine Escoffre, Bertrand Arnulf, Margaret Macro, Karim Belhadj, Laurent Garderet, Murielle Roussel, Catherine Payen, Claire Mathiot, Jean P Fermand, Nathalie Meuleman, Sandrine Rollet, Michelle E Maglio, Andrea A Zeytoonjian, Edie A Weller, Nikhil Munshi, Kenneth C Anderson, Paul G Richardson, Thierry Facon, Hervé Avet-Loiseau, Jean-Luc Harousseau, Philippe Moreau
BACKGROUND: High-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation. METHODS: We randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients)...
April 6, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28317148/bortezomib-induced-peripheral-neuropathy-a-genome-wide-association-study-on-multiple-myeloma-patients
#18
Chiara Campo, Miguel Inacio da Silva Filho, Niels Weinhold, Seyed Hamidreza Mahmoudpour, Hartmut Goldschmidt, Kari Hemminki, Maximilian Merz, Asta Försti
The proteasome-inhibitor bortezomib was introduced into the treatment of multiple myeloma more than a decade ago. It is clinically beneficial, but peripheral neuropathy (PNP) is a side effect that may limit its use in some patients. To examine the possible genetic predisposing factors to PNP, we performed a genome-wide association study on 646 bortezomib-treated German multiple myeloma patients. Our aim was to identify genetic risk variants associated with the development of PNP as a serious side effect of the treatment...
March 20, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28286483/long-term-effects-pathophysiological-mechanisms-and-risk-factors-of-chemotherapy-induced-peripheral-neuropathies-a-comprehensive-literature-review
#19
REVIEW
Nicolas Kerckhove, Aurore Collin, Sakahlé Condé, Carine Chaleteix, Denis Pezet, David Balayssac
Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28280389/update-on-the-optimal-use-of-bortezomib-in-the-treatment-of-multiple-myeloma
#20
REVIEW
Meera Mohan, Aasiya Matin, Faith E Davies
The proteasome inhibitor (PI) "bortezomib" has now been in routine clinical practice for over a decade. It is now considered an important backbone therapy for all stages of the disease, and data continue to grow to support its use in newly diagnosed patients, relapsed and relapsed/refractory disease, maintenance therapy, high risk, and renal failure. Much has been learnt about the most clinically effective way of delivering therapy, with patients often benefiting more from a triplet bortezomib combination compared to a doublet combination...
2017: Cancer Management and Research
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