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https://www.readbyqxmd.com/read/28723725/meningeal-melanomatosis-following-discontinuation-of-dabrafenib-implications-for-the-maintenance-of-long-term-complete-remission
#1
Victoria Grätz, Nadine Lüttmann, Ozan Haase, Ewan A Langan, André Kemmling, Detlef Zillikens, Patrick Terheyden
A subset of 10-20% of patients under continuous BRAF inhibitor monotherapy achieve long-term progression-free and overall survival. Definitive criteria for the safe cessation of BRAF inhibitor monotherapy in treatment-responsive melanoma patients are lacking. We report a patient who remained in complete remission (CR) for 5 years under dabrafenib. The treatment was withdrawn because of concerns about cardiac toxicity. Four months thereafter the patient developed neurological symptoms, including diplopia and bilateral visual loss...
July 18, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28716527/identification-of-a-synergistic-combination-of-smac-mimetic-and-bortezomib-to-trigger-cell-death-in-b-cell-non-hodgkin-lymphoma-cells
#2
Irfan Ahmed Bhatti, Behnaz Ahangarian Abhari, Simone Fulda
Recently, copy number gains and increased expression levels of cIAP1 and cIAP2 have been reported in B-cell non-Hodgkin lymphomas (NHL). Therefore, we investigated the therapeutic potential of the Smac mimetic BV6 that antagonizes cIAP1/2 and XIAP. Here, we discover that subtoxic concentrations of BV6 prime B-cell NHL cells to proteasome inhibitor Bortezomib-induced cell death. Synergistic induction of cell death by BV6 and Bortezomib is confirmed by calculation of combination index in different cell lines, emphasizing the broader relevance of this combination...
July 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28711086/the-new-paradigm-of-systemic-therapies-for-metastatic-melanoma
#3
REVIEW
Virginia O Volpe, Daniel M Klufas, Upendra Hegde, Jane M Grant-Kels
New treatments for metastatic melanoma work through distinct mechanisms: enhancing the immune response and blocking cellular proliferation. Agents that enhance the immune response include ipilimumab, pembrolizumb, and nivolumab; agents that block cellular proliferation include vemurafenib, dabrafenib, trametinib, cobimetinib, binimetinib, and selumetinib. The translational impact of laboratory discoveries has revolutionized management of metastatic melanoma and enhanced the prognosis of affected patients.
August 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28709799/trough-dabrafenib-plasma-concentrations-can-predict-occurrence-of-adverse-events-requiring-dose-reduction-in-metastatic-melanoma
#4
Marine Rousset, Caroline Dutriaux, Pauline Bosco-Lévy, Sorilla Prey, Anne Pham-Ledard, Léa Dousset, Emilie Gérard, Stephane Bouchet, Mireille Canal-Raffin, Karine Titier, Mathieu Molimard
INTRODUCTION: Dabrafenib and trametinib bitherapy provides significant benefits in BRAFV600(mut) metastatic melanoma patients; however, adverse events (AE) occur, leading to dose reduction in 33% of patients. We aimed to investigate a relation between plasma dabrafenib and trametinib concentrations and occurrence of AE. METHODS: Plasma samples from metastatic BRAFV600(mut) melanoma patients treated with dabrafenib±trametinib were prospectively collected at trough concentration before any dose reduction...
July 12, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28707403/melanocytic-lesion-evolution-patterns-with-targeted-therapies-and-immunotherapies-for-advanced-metastatic-melanoma-an-observational-study
#5
Cathy Yunjia Zhao, Shelley Ji Eun Hwang, Deepal Wakade, Giuliana Carlos, Rachael Anforth, Pablo Fernández-Peñas
BACKGROUND/OBJECTIVES: Various cutaneous side-effects have been reported with anti-melanoma systemic therapies. This study investigated the changes in melanocytic lesion pigmentation in patients on four different therapies. METHODS: We analysed the serial dermatoscopic photographs of atypical melanocytic lesions taken from patients with advanced metastatic melanoma on four different systemic therapies (selective BRAF-inhibitor monotherapy, dabrafenib combined with trametinib [D&T], anti-programmed cell death protein 1 [anti-PD1] therapies, and anti-PD1 combined with ipilimumab) seen from February 2013 to May 2016...
July 14, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28695986/acute-heart-failure-as-a-result-of-granulomatous-myocarditis-case-report-on-a-patient-with-metastatic-melanoma-treated-with-dabrafenib-and-trametinib
#6
J K Winkler, K Buder-Bakhaya, E Ellert, E Herpel, U M Martens, A Enk, J C Hassel
Treatment options for metastatic melanoma have changed substantially in recent years. Targeting immune checkpoints has improved prognosis of melanoma patients. For melanomas harboring BRAF mutations, inhibition of the mitogen-activated protein kinase pathway is a promising therapeutic option. Combined BRAF and MEK inhibition improves progression-free and overall survival. This article is protected by copyright. All rights reserved.
July 11, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28684402/braf-v600-inhibition-alters-the-microrna-cargo-in-the-vesicular-secretome-of-malignant-melanoma-cells
#7
Taral R Lunavat, Lesley Cheng, Berglind O Einarsdottir, Roger Olofsson Bagge, Somsundar Veppil Muralidharan, Robyn A Sharples, Cecilia Lässer, Yong Song Gho, Andrew F Hill, Jonas A Nilsson, Jan Lötvall
The BRAF inhibitors vemurafenib and dabrafenib can be used to treat patients with metastatic melanomas harboring BRAF(V600) mutations. Initial antitumoral responses are often seen, but drug-resistant clones with reactivation of the MEK-ERK pathway soon appear. Recently, the secretome of tumor-derived extracellular vesicles (EVs) has been ascribed important functions in cancers. To elucidate the possible functions of EVs in BRAF-mutant melanoma, we determined the RNA content of the EVs, including apoptotic bodies, microvesicles, and exosomes, released from such cancer cells after vemurafenib treatment...
July 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28652244/targeting-adenosine-in-braf-mutant-melanoma-reduces-tumor-growth-and-metastasis
#8
Arabella Young, Shin Foong Ngiow, Jason Madore, Julia Reinhardt, Jennifer Landsberg, Arash Chitsazan, Jai Rautela, Tobias Bald, Deborah Barkauskas, Elizabeth Ahern, Nicholas Huntington, Dirk Schadendorf, Georgina V Long, Glen M Boyle, Michael Hölzel, Richard A Scolyer, Mark J Smyth
Increasing evidence exists for the role of immunosuppressive adenosine in promoting tumor growth and spread in a number of cancer types, resulting in poor clinical outcomes. In this study, we assessed whether the CD73-adenosinergic pathway is active in melanoma patients and whether adenosine restricts the efficacy of clinically approved targeted therapies for commonly mutated BRAF(V600E) melanoma. In AJCC Stage III melanoma patients, CD73 expression (the enzyme that generates adenosine) correlated significantly with patients presenting nodal metastatic melanoma, suggesting that targeting this pathway may be effective in advanced stage disease...
June 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28648698/three-year-pooled-analysis-of-factors-associated-with-clinical-outcomes-across-dabrafenib-and-trametinib-combination-therapy-phase-3-randomised-trials
#9
Dirk Schadendorf, Georgina V Long, Daniil Stroiakovski, Boguslawa Karaszewska, Axel Hauschild, Evgeny Levchenko, Vanna Chiarion-Sileni, Jacob Schachter, Claus Garbe, Caroline Dutriaux, Helen Gogas, Mario Mandalà, John B A G Haanen, Céleste Lebbé, Andrzej Mackiewicz, Piotr Rutkowski, Jean-Jacques Grob, Paul Nathan, Antoni Ribas, Michael A Davies, Ying Zhang, Mathilde Kaper, Bijoyesh Mookerjee, Jeffrey J Legos, Keith T Flaherty, Caroline Robert
AIM: Understanding predictors of long-term benefit with currently available melanoma therapies is the key for optimising individualised treatments. A prior pooled analysis of dabrafenib plus trametinib (D + T)-randomised trials (median follow-up, 20.0 months) identified baseline lactate dehydrogenase (LDH) and number of organ sites with metastasis as predictive factors for progression-free (PFS) and overall (OS) survival. However, longer-term follow-up analyses are needed to confirm which patients treated with D + T can achieve maximum benefit...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28628251/a-network-meta-analysis-of-short-and-long-term-efficacy-of-targeted-therapy-with-single-or-double-drug-regimens-in-the-treatment-of-stage-iii-iv-malignant-melanoma-based-on-16-randomized-controlled-trials
#10
Ting Xie, Chun-Yu Huang, Xu Kang, Jia-Sheng Luo, Xiao-Min Qin, Feng Han
For the treatment of stage III/IV malignant melanoma (MM), a network meta-analysis (NMA) was conducted to compare the short and long-term efficacy of targeted therapy with single or double-drug regimens. All conducted randomized controlled trials (RCTs) searched from PubMed and Cochrane Library were included in the study for direct and indirect comparison for MM. The odds ratio (OR) and surface under the cumulative ranking curves (SUCRA) value of the targeted therapy with single or double-drug regimens for treatment of stage III/IV MM were also analyzed...
June 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28626033/dabrafenib-plus-trametinib-achieves-overall-and-intracranial-responses
#11
(no author information available yet)
Dabrafenib plus trametinib achieves intracranial responses in BRAF-mutant melanoma brain metastases.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28614138/acute-exudative-paraneoplastic-polymorphous-vitelliform-maculopathy-during-vemurafenib-and-pembrolizumab-treatment-for-metastatic-melanoma
#12
Harpal S Sandhu, Anton M Kolomeyer, Marisa K Lau, Carol L Shields, Lynn M Schuchter, Charles W Nichols, Tomas S Aleman
PURPOSE: To describe a patient with BRAF mutation-positive cutaneous melanoma who developed acute exudative polymorphous vitelliform maculopathy during vemurafenib and pembrolizumab treatment for metastatic melanoma. METHODS: Retrospective case report documented with wide-field fundus imaging, spectral domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: A 55-year-old woman with bilateral ductal breast carcinoma and BRAF mutation-positive metastatic cutaneous melanoma complained of bilateral blurred vision within 5 days of starting vemurafenib (BRAF inhibitor)...
June 13, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28611627/panniculitis-associated-with-mek-inhibitor-therapy-an-uncommon-adverse-effect
#13
Miruna Negulescu, Florian Deilhes, Vincent Sibaud, Emilie Tournier, Laurence Lamant, Serge Boulinguez, Nicolas Meyer
The combination of MEK inhibitor (cobimetinib, trametinib) and BRAF inhibitor (vemurafenib, dabrafenib) is now the first-line treatment in patients with BRAF V600-mutated metastatic melanoma. This association reduces cutaneous adverse events induced by BRAF inhibitors alone, including photosensitivity, hand-foot syndrome, hyperkeratosis, alopecia, skin papillomas, keratoacanthomas, and squamous-cell carcinomas. While panniculitis has exceptionally been reported with BRAF inhibitors, this rare side effect has never been described with the use of MEK inhibitors...
January 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28608286/survival-of-melanoma-patients-treated-with-novel-drugs-retrospective-analysis-of-real-world-data
#14
Marta Polkowska, Paweł Ekk-Cierniakowski, Edyta Czepielewska, Wojciech Wysoczański, Wojciech Matusewicz, Małgorzata Kozłowska-Wojciechowska
PURPOSE: Recently, several new drugs have been licensed for advanced melanoma therapy, significantly changing the therapeutic landscape. Ipilimumab and vemurafenib were the first drugs that demonstrated a survival benefit over the long-standing standard therapy with dacarbazine. However, the comparative efficacy of these novel drugs has not been properly assessed yet. PATIENTS AND METHODS: We conducted a retrospective analysis of all the Polish population treated between January 2012 and October 2016 with one of the following agents: ipilimumab (IPI), vemurafenib (VEM), dabrafenib (DAB), and classic chemotherapy (CTH)...
June 12, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28592387/dabrafenib-plus-trametinib-in-patients-with-braf-v600-mutant-melanoma-brain-metastases-combi-mb-a-multicentre-multicohort-open-label-phase-2-trial
#15
Michael A Davies, Philippe Saiag, Caroline Robert, Jean-Jacques Grob, Keith T Flaherty, Ana Arance, Vanna Chiarion-Sileni, Luc Thomas, Thierry Lesimple, Laurent Mortier, Stergios J Moschos, David Hogg, Iván Márquez-Rodas, Michele Del Vecchio, Céleste Lebbé, Nicolas Meyer, Ying Zhang, Yingjie Huang, Bijoyesh Mookerjee, Georgina V Long
BACKGROUND: Dabrafenib plus trametinib improves clinical outcomes in BRAF(V600)-mutant metastatic melanoma without brain metastases; however, the activity of dabrafenib plus trametinib has not been studied in active melanoma brain metastases. Here, we report results from the phase 2 COMBI-MB trial. Our aim was to build on the current body of evidence of targeted therapy in melanoma brain metastases through an evaluation of dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases...
June 2, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28567600/dabrafenib-therapy-in-30-patients-with-melanoma-metastatic-to-the-brain-a-single-centre-controlled-retrospective-study-in-hungary
#16
Eszter Gorka, Dániel Fabó, András Gézsi, Kata Czirbesz, Imre Fedorcsák, Gabriella Liszkay
Dabrafenib is a potent BRAF inhibitor, which showed intracranial tumor activity. The purpose of our retrospective analysis was to evaluate the efficacy of dabrafenib for patients with melanoma brain metastasis (BM). We studied 30 BRAF mutant melanoma patients with BM, who received dabrafenib after local control of the brain between 2014 and 2017. Eastern Cooperative Oncology Group Performance Status (ECOG) was 0-2. The control arm consisted of 204 melanoma patients from our institutional melanoma database with BM and ECOG 0-2 treated with local therapies and/or chemotherapy, between 2003 and 2015...
June 1, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28557366/radiosensitization-by-braf-inhibitors
#17
Sophia Boyoung Strobel, Sylvie Pätzold, Lisa Zimmer, Alexandra Jensen, Alexander Enk, Jessica Cecile Hassel
BACKGROUND: Increased skin toxicity during combination therapy with a BRAF inhibitor and radiation therapy has recently been reported. MATERIAL AND METHODS: We present seven melanoma patients with non-resectable stage III or IV disease and concomitant treatment with a BRAF inhibitor and radiation therapy. RESULTS: In all patients, combination therapy yielded a good local response. Only two patients, both on vemurafenib, showed severe radiation dermatitis (CTCAE grade 3/4) after one and two weeks, respectively, resulting in interruption of BRAF inhibitor treatment...
May 30, 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28553668/the-clinical-spectrum-of-erdheim-chester-disease-an-observational-cohort-study
#18
Juvianee I Estrada-Veras, Kevin J O'Brien, Louisa C Boyd, Rahul H Dave, Benjamin Durham, Liqiang Xi, Ashkan A Malayeri, Marcus Y Chen, Pamela J Gardner, Jhonell R Alvarado-Enriquez, Nikeith Shah, Omar Abdel-Wahab, Bernadette R Gochuico, Mark Raffeld, Elaine S Jaffe, William A Gahl
Erdheim-Chester Disease (ECD) is a rare, potentially fatal, multi-organ myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a-, and frequently S100-. The purpose of this report is to describe the clinical and molecular variability of ECD. Sixty consecutive ECD patients (45 males, 15 females) were prospectively evaluated at the NIH Clinical Center between 2011 and 2015. Comprehensive imaging and laboratory studies were performed, and tissues were examined for BRAF V600E and MAPK pathway mutations...
February 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#19
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28537004/mek-inhibitors-in-the-treatment-of-metastatic-melanoma-and-solid-tumors
#20
REVIEW
Antonio M Grimaldi, Ester Simeone, Lucia Festino, Vito Vanella, Martina Strudel, Paolo A Ascierto
The mitogen-activated protein kinase (MAPK) cascade is an intracellular signaling pathway involved in the regulation of cellular proliferation and the survival of tumor cells. Several different mutations, involving BRAF or NRAS, exert an oncogenic effect by activating the MAPK pathway, resulting in an increase in cellular proliferation. These mutations have become targets for new therapeutic strategies in melanoma and other cancers. Selective MEK inhibitors have the ability to inhibit growth and induce cell death in BRAF- and NRAS-mutant melanoma cell lines...
May 23, 2017: American Journal of Clinical Dermatology
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