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bortezomib neuropathy

Shigeo Hashimoto, Takashi Kuroha, Toshio Yano, Naoko Sato, Tatsuo Furukawa
Five cases were treated by adding daily low-dose thalidomide (50 mg) to bortezomib and dexamethasone therapy for refractory multiple myeloma. This therapy was effective in four cases, with an improvement of bone pain and regression of M-protein. One case was treated with cyclophosphamide, thalidomide, and dexamethasone, adding bortezomib after starting the three-drug combination therapy. This patient has remained in a stable disease state since the beginning of this therapy. Regarding the other four cases, a partial response and a prolonged survival for approximately one year were noted...
2016: Internal Medicine
Daolin Wei, Yin Tong, Haitao Bai, Qi Cai, Yanrong Gao, Chun Wang
BACKGROUND: The purpose of the current study was to evaluate the efficacy and safety of a dose increased weekly Bortezomib (Bor) based combination therapy in multiple myeloma (MM) patients. RESULTS: The overall response rate (ORR) in the modified Bor group was 76.6%, composed of 40% complete response (CR), 3.3% very good partial response (VGPR) and 33.3% partial response (PR). The ORR was 82.3%, with 26.5% CR, 5.9% VGPR and 50% PR in control. A subgroup analysis showed both groups had equal efficacy in newly diagnosed MM patients ( P = 1...
September 21, 2016: Oncotarget
Ramón García-Sanz, Luis Antonio Corchete, Miguel Alcoceba, María Carmen Chillon, Cristina Jiménez, Isabel Prieto, María García-Álvarez, Noemi Puig, Immaculada Rapado, Santiago Barrio, Albert Oriol, María Jesús Blanchard, Javier de la Rubia, Rafael Martínez, Juan José Lahuerta, Marcos González Díaz, María Victoria Mateos, Jesús Fernando San Miguel, Joaquín Martínez-López, María Eugenia Sarasquete
Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide...
September 8, 2016: Hematological Oncology
Noa Biran, Scott D Rowley, David H Vesole, Shijia Zhang, Michele L Donato, Joshua Richter, Alan P Skarbnik, Andrew Pecora, David S Siegel
Escalating doses of bortezomib with high-dose melphalan was evaluated as as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory multiple myeloma (MM). MM patients with less than a partial remission (PR) (or 50% reduction) compared to their pretransplantation paraprotein parameters after a prior ASCT with melphalan conditioning, or who were in relapse after a prior autologous transplantation, were eligible for study. Bortezomib was dose escalated in steps of 1, 1...
August 31, 2016: Biology of Blood and Marrow Transplantation
Maximilian Merz, Hans Salwender, Mathias Haenel, Elias K Mai, Uta Bertsch, Christina Kunz, Thomas Hielscher, Igor W Blau, Christof Scheid, Dirk Hose, Anja Seckinger, Anna Jauch, Jens Hillengass, Marc S Raab, Baerbel Schurich, Markus Munder, Peter Brossart, Christian Gerecke, Hans-Walter Lindemann, Matthias Zeis, Katja Weisel, Jan Duerig, Hartmut Goldschmidt
No abstract text is available yet for this article.
August 18, 2016: Haematologica
Morie A Gertz
DISEASE OVERVIEW: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, peripheral/autonomic neuropathy, and atypical multiple myeloma. DIAGNOSIS: Tissue biopsy stained with Congo red demonstrating amyloid deposits with applegreen birefringence is required for diagnosis...
September 2016: American Journal of Hematology
S Expósito Vizcaíno, J Casanova-Mollà, L Escoda, S Galán, J Miró
INTRODUCTION: The neuropathic pain is the most habitual problem in the neuropathy induced by chemotherapy (NIQ) and the one that more interferes in the quality of life of the patients. His precocious detection turns out to be fundamental to reduce or to eliminate the problems that from this one stem. The aims of this study were: 1) determine the incident and NIQ's characteristics and neuropathic pain in patients with mieloma multiple (MM) treated with bortezomib, and 2) to evaluate the impact of the neuropathic pain in the activities of the daily life (AVD)...
July 27, 2016: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Adam J Olszewski, Steven P Treon, Jorge J Castillo
INTRODUCTION: Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM) is a rare lymphoma affecting older patients. Its management largely relies on small phase II trials and it is unclear how their results translate into clinical practice in the community. METHOD: We evaluated changes in the presentation, management, and survival among 2,666 Medicare beneficiaries diagnosed with WM between 1994 and 2011, using Medicare claims linked to Surveillance, Epidemiology and End Results data...
July 29, 2016: Oncologist
Lifeng Yang, Juefeng Wan, Sheng Xiao, Darryll Barkhouse, Ji Zhu, Guichao Li, Bo Lu, Zhen Zhang
The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines...
2016: American Journal of Cancer Research
Chiara Campo, Miguel Inacio Da Silva Filho, Niels Weinhold, Hartmut Goldschmidt, Kari Hemminki, Maximilian Merz, Asta Försti
The introduction of proteasome inhibitors in the treatment of multiple myeloma (MM) patients has been a therapeutic success. Peripheral neuropathy (PNP) remains one of the most frequent side-effects experienced by patients who receive these novel agents. Recent investigations on the mechanisms of PNP in patients treated with bortezomib have suggested genetic susceptibility to neurotoxicity. We used data from a genome-wide association study conducted on 646 bortezomib-treated German MM patients to replicate the previously reported associations between single-nucleotide polymorphisms (SNPs) in candidate genes and PNP in MM patients, including 298 SNPs with a nominal significance (p value <0...
July 16, 2016: Neurochemical Research
Ayumu Matsuoka, Ayako Mitsuma, Osamu Maeda, Hiroaki Kajiyama, Hitoshi Kiyoi, Yasuhiro Kodera, Masato Nagino, Hidemi Goto, Yuichi Ando
Chemotherapy-induced peripheral neurotoxicity (CIPN) seriously impairs patients' quality of life cumulatively and dose-dependently. Because assessment of CIPN usually depends on patients' subjective evaluation of symptoms, objective and quantitative measures are needed. We evaluated a point-of-care nerve conduction device (POCD), previously validated for the assessment of diabetic peripheral neuropathy. Sensory nerve action potential (SNAP) amplitude and sensory nerve conduction velocity (SNCV) of the sural nerve were measured using a portable, automated POCD (DPNCheck(®) , NeuroMetrix Inc...
July 14, 2016: Cancer Science
Donna E Reece, Young Trieu, Esther Masih-Khan, Eshetu G Atenafu, Christine Chen, Anca Prica, Rodger Tiedemann, Suzanne Trudel, Vishal Kukreti
INTRODUCTION: Cyclophosphamide, bortezomib, and prednisone (CyBorP) is a highly effective, well-tolerated regimen in relapsed/refractory multiple myeloma. CyBorP, originally developed at our center to include weekly bortezomib (Bor) and alternate-day prednisone (P), was recently modified so that weekly dexamethasone (D) replaced prednisone. PATIENTS AND METHODS: To assess the effectiveness and tolerability of CyBorP/D in real-world practice, we identified 96 relapsed/refractory patients who received ≥ 1 28-day cycle of CyBorP/D, consisting of cyclophosphamide 300 mg/m(2) (days 1, 8, 15, and 22), Bor 1...
July 2016: Clinical Lymphoma, Myeloma & Leukemia
T B M Castro, A E Hallack Neto, A Atalla, L C Ribeiro
In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61%) vs 23 (39%) males, and of whites, 49 (83.1%) vs 10 (16.9%) blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6). Regarding staging at diagnosis, 27 (45...
2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Meletios A Dimopoulos, Antonio Palumbo, Paolo Corradini, Michele Cavo, Michel Delforge, Francesco Di Raimondo, Katja C Weisel, Albert Oriol, Markus Hansson, Angelo Vacca, María Jesús Blanchard, Hartmut Goldschmidt, Chantal Doyen, Martin Kaiser, Mario Petrini, Pekka Anttila, Anna Maria Cafro, Reinier Raymakers, Jesus San-Miguel, Felipe de Arriba, Stefan Knop, Christoph Röllig, Enrique M Ocio, Gareth Morgan, Neil Miller, Mathew Simcock, Teresa Peluso, Jennifer Herring, Lars Sternas, Mohamed H Zaki, Philippe Moreau
Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day cycles with low-dose dexamethasone 40 mg (20 mg for patients aged >75 years) on days 1, 8, 15, and 22 until progressive disease or unacceptable toxicity...
July 28, 2016: Blood
Albert Alé, Jordi Bruna, Aina Calls, Maria Karamita, Sylva Haralambous, Lesley Probert, Xavier Navarro, Esther Udina
Bortezomib is a proteasome inhibitor with a remarkable antitumor activity, used in the clinic as first line treatment for multiple myeloma. One hallmark of bortezomib mechanism of action in neoplastic cells is the inhibition of nuclear factor kappa B (NFκB), a transcription factor involved in cell survival and proliferation. Bortezomib-induced peripheral neuropathy is a dose-limiting toxicity that often requires adjustment of treatment and affects patient's prognosis and quality of life. Since disruption of NFκB pathway can also affect neuronal survival, we assessed the role of NFκB in bortezomib-induced neuropathy by using a transgenic mouse that selectively provides blockage of the NFκB pathway in neurons...
July 2016: Neurotoxicology
Muhammad Bilal Abid, Sanjay De Mel, Muhammad Abbas Abid, Kong Bing Tan, Wee Joo Chng
BACKGROUND: Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. CASE PRESENTATION: A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance...
July 2, 2016: Cancer Biology & Therapy
Kathleen Scott, Patrick J Hayden, Andrea Will, Keith Wheatley, Imelda Coyne
BACKGROUND: Multiple myeloma is a malignancy of plasma cells accounting for approximately 1% of cancers and 12% of haematological malignancies. The first-in-class proteasome inhibitor, bortezomib, is commonly used to treat newly diagnosed as well as relapsed/refractory myeloma, either as single agent or combined with other therapies. OBJECTIVES: We conducted a systematic review and meta-analysis to assess the effects of bortezomib on overall survival (OS), progression-free survival (PFS), response rate (RR), health-related quality of life (HRQoL), adverse events (AEs) and treatment-related death (TRD)...
2016: Cochrane Database of Systematic Reviews
Alhasan Elghouche, Tom Shokri, Yewen Qin, Susannah Wargo, Deborah Citrin, Carter Van Waes
We report a constellation of cervical polyneuropathies in a patient treated with concurrent bortezomib, cetuximab, and cisplatin alongside intensity modulated radiotherapy for carcinoma of the tonsil with neck metastasis. The described deficits include brachial plexopathy, cervical sensory neuropathy, and oculosympathetic, recurrent laryngeal, and phrenic nerve palsies within the ipsilateral radiation field. Radiation neuropathy involving the brachial plexus is typically associated with treatment of breast or lung cancer; however, increased awareness of this entity in the context of investigational agents with potential neuropathic effects in head and neck cancer has recently emerged...
2016: Case Reports in Otolaryngology
Florence Magrangeas, Rowan Kuiper, Hervé Avet-Loiseau, Wilfried Gouraud, Catherine Guérin-Charbonnel, Ludovic Ferrer, Alexandre Aussem, Haytham Elghazel, Jérôme Suhard, Henri Der Sakissian, Michel Attal, Nikhil C Munshi, Pieter Sonneveld, Charles Dumontet, Philippe Moreau, Mark van Duin, Loïc Campion, Stéphane Minvielle
PURPOSE: Painful peripheral neuropathy is a frequent toxicity associated with bortezomib therapy. This study aimed to identify loci that affect susceptibility to this toxicity. EXPERIMENTAL DESIGN: A genome-wide association study (GWAS) of 370,605 SNPs was performed to identify risk variants for developing severe bortezomib-induced peripheral neuropathy (BiPN) in 469 patients with multiple myeloma who received bortezomib-dexamethasone therapy prior to autologous stem cell in randomized clinical trials of the Intergroupe Francophone du Myelome (IFM) and findings were replicated in 114 patients with multiple myeloma of the HOVON-65/GMMG-HD4 clinical trial...
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Holly L Hopkins, Natalie A Duggett, Sarah J L Flatters
PURPOSE OF REVIEW: Chemotherapy-induced painful neuropathy (CIPN) is a major dose-limiting side-effect of several widely used chemotherapeutics. Rodent models of CIPN have been developed using a range of dosing regimens to reproduce pain-like behaviours akin to patient-reported symptoms. This review aims to connect recent evidence-based suggestions for clinical treatment to preclinical data. RECENT FINDINGS: We will discuss CIPN models evoked by systemic administration of taxanes (paclitaxel and docetaxel), platinum-based agents (oxaliplatin and cisplatin), and the proteasome-inhibitor - bortezomib...
June 2016: Current Opinion in Supportive and Palliative Care
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