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https://www.readbyqxmd.com/read/28453695/genetic-variants-of-dna-repair-related-genes-predict-efficacy-of-tas-102-in-patients-with-refractory-metastatic-colorectal-cancer
#1
M Suenaga, M Schirripa, S Cao, W Zhang, D Yang, S Murgioni, D Rossini, F Marmorino, A Mennitto, Y Ning, S Okazaki, M D Berger, Y Miyamoto, R Gopez, A Barzi, T Yamaguchi, F Loupakis, H-J Lenz
Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#2
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28447051/regorafenib-in-gastric-cancer
#3
EDITORIAL
Elizabeth C Smyth
No abstract text is available yet for this article.
2017: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28437801/-regorafenib-a-revolution-in-the-systemic-treatment-options-of-hcc
#4
Jan Bornschein, Sophie Schlosser
No abstract text is available yet for this article.
April 24, 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/28422839/unexpected-side-effect-in-mcrc-a-care-compliant-case-report-of-regorafenib-induced-hyperammonemic-encephalopathy
#5
Michela Quirino, Sabrina Rossi, Giovanni Schinzari, Michele Basso, Antonia Strippoli, Alessandra Cassano, Carlo Barone
RATIONALE: Regorafenib represents a treatment option in heavily pretreated patients affected by metastatic colorectal cancer (mCRC). Its safety profile is typical of small-molecule tyrosine-kinase inhibitors (TKIs) and most adverse events are manageable. PATIENT CONCERNS: A 56 years-old Caucasian man affected by mCRC with normal hepatic reserve was treated with regorafenib as second-line treatment. After only 2 days of therapy, the patient presented to the emergency department due to impairment of both spatial and temporal orientation and motor function with bradylalia...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28422758/first-in-human-trial-of-multikinase-vegf-inhibitor-regorafenib-and-anti-egfr-antibody-cetuximab-in-advanced-cancer-patients
#6
Vivek Subbiah, Muhammad Rizwan Khawaja, David S Hong, Behrang Amini, Jiang Yungfang, Hui Liu, Adrienne Johnson, Alexa B Schrock, Siraj M Ali, James X Sun, David Fabrizio, Sarina Piha-Paul, Siqing Fu, Apostolia M Tsimberidou, Aung Naing, Filip Janku, Daniel D Karp, Michael Overman, Cathy Eng, Scott Kopetz, Funda Meric-Bernstam, Gerald S Falchook
BACKGROUND: The combination of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab overcomes intrinsic and acquired resistance in both EGFR-sensitive and EGFR-resistant preclinical models of colorectal cancer (CRC). METHODS: Utilizing a standard 3+3 design, a phase I study was designed to determine safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) of the regorafenib plus cetuximab combination among patients with advanced cancer including CRC...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28420805/immunotherapeutic-approaches-for-hepatocellular-carcinoma
#7
Vito Longo, Antonio Gnoni, Andrea Casadei Gardini, Salvatore Pisconti, Antonella Licchetta, Mario Scartozzi, Riccardo Memeo, Vincenzo Ostilio Palmieri, Giuseppe Aprile, Daniele Santini, Patrizia Nardulli, Nicola Silvestris, Oronzo Brunetti
Hepatocellular carcinoma (HCC) is a cancer with a high mortality rate due to the fact that the diagnosis usually occurs at anadvanced stage. Even in case of curative surgical treatment, recurrence is common. Sorafenib and regorafenib are the only therapeutic agents that have been demonstrated to be effective in advanced HCC, thus novel curative approaches are urgently needed. Recent studies focus on the role of immune system in HCC. In fact, the unique immune response in the liver favors tolerance, which can represent a real challenge for conventional immunotherapy in these patients...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398282/the-role-of-regorafenib-in-hepatocellular-carcinoma
#8
Catherine T Frenette
No abstract text is available yet for this article.
February 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28378839/off-target-effects-and-clinical-outcome-in-metastatic-colorectal-cancer-patients-receiving-regorafenib-the-tribute-analysis
#9
Riccardo Giampieri, Michela Del Prete, Tiziana Prochilo, Marco Puzzoni, Valeria Pusceddu, Fabiana Pani, Elena Maccaroni, Roberta Mascia, Maria Giuditta Baleani, Tania Meletani, Rossana Berardi, Anna Maria Lanzillo, Stefano Mariotti, Alberto Zaniboni, Stefano Cascinu, Mario Scartozzi
Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28361439/cost-effectiveness-analysis-of-regorafenib-for-gastrointestinal-stromal-tumour-gist-in-germany
#10
David Tamoschus, Katja Draexler, Jane Chang, Christopher Ngai, Matthew Madin-Warburton, Ashley Pitcher
BACKGROUND: No study has compared the cost-effectiveness of active treatment options for unresectable or metastatic gastrointestinal stromal tumours in patients who progressed on or are intolerant to prior treatment with imatinib and sunitinib. The aim of this study was to estimate the cost-effectiveness of regorafenib compared to imatinib rechallenge in this setting in Germany. METHODS: Hazard ratios for progression-free (PFS) and overall survival (OS) with regorafenib versus imatinib rechallenge were estimated by indirect comparison...
March 30, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28351781/geis-guidelines-for-gastrointestinal-sarcomas-gist
#11
REVIEW
Andrés Poveda, Xavier García Del Muro, Jose Antonio López-Guerrero, Ricardo Cubedo, Virginia Martínez, Ignacio Romero, César Serrano, Claudia Valverde, Javier Martín-Broto
Gastrointestinal stromal sarcomas (GISTs) are the most common mesenchymal tumours originating in the digestive tract. They have a characteristic morphology, are generally positive for CD117 (c-kit) and are primarily caused by activating mutations in the KIT or PDGFRA genes(1). On rare occasions, they occur in extravisceral locations such as the omentum, mesentery, pelvis and retroperitoneum. GISTs have become a model of multidisciplinary work in oncology: the participation of several specialties (oncologists, pathologists, surgeons, molecular biologists, radiologists…) has forested advances in the understanding of this tumour and the consolidation of a targeted therapy, imatinib, as the first effective molecular treatment in solid tumours...
March 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28345929/utility-of-cyp3a4-and-pxr-car-cyp3a4-3a7-transgenic-mouse-models-to-assess-the-magnitude-of-cyp3a4-mediated-drug-drug-interactions
#12
Justin Q Ly, Kirsten Messick, Ann Qin, Ryan H Takahashi, Edna F Choo
Species differences in the expression, activity, regulation, and substrate specificity of metabolizing enzymes preclude the use of animal models to predict clinical drug-drug interactions (DDIs). The objective of this work is to determine if the transgenic (Tg) Cyp3a(-/-)Tg-3A4Hep/Int and Nr1i2/Nr1i3(-/-)-Cyp3a(-/-)Tg-PXR-CAR-3A4/3A7Hep/Int (PXR-CAR-CYP3A4/3A7) mouse models could be used to predict in vivo DDI of 10 drugs; alprazolam, bosutinib, crizotinib, dasatinib, gefitinib, ibrutinib, regorafenib, sorafenib, triazolam, and vandetinib (as victims); with varying magnitudes of reported CYP3A4 clinical DDI...
April 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28321172/gastrointestinal-stromal-tumor-of-the-stomach-with-axillary-lymph-node-metastasis-a-case-report
#13
Naoki Kubo, Nobumichi Takeuchi
Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors, although metastasis to the perigastric lymph nodes is relatively rare, compared with liver or peritoneal metastasis. In this report, we describe a case of stomach GIST with a solitary simultaneous metastasis in the left axillary lymph node. A 68-year-old man was diagnosed with a large upper-stomach GIST, and computed tomography and positron emission tomography revealed masses in the left axilla and right mediastinum...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28302530/regorafenib-overcomes-chemotherapeutic-multidrug-resistance-mediated-by-abcb1-transporter-in-colorectal-cancer-in%C3%A2-vitro-and-in%C3%A2-vivo-study
#14
Yi-Jun Wang, Yun-Kai Zhang, Guan-Nan Zhang, Sweilem B Al Rihani, Meng-Ning Wei, Pranav Gupta, Xiao-Yu Zhang, Suneet Shukla, Suresh V Ambudkar, Amal Kaddoumi, Zhi Shi, Zhe-Sheng Chen
Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1...
June 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28295221/regosarc-regorafenib-versus-placebo-in-doxorubicin-refractory-soft-tissue-sarcoma-a-quality-adjusted-time-without-symptoms-of-progression-or-toxicity-analysis
#15
Vincent Berry, Laurent Basson, Emilie Bogart, Olivier Mir, Jean-Yves Blay, Antoine Italiano, François Bertucci, Christine Chevreau, Stéphanie Clisant-Delaine, Bernadette Liegl-Antzager, Emmanuelle Tresch-Bruneel, Jennifer Wallet, Sophie Taieb, Emilie Decoupigny, Axel Le Cesne, Thomas Brodowicz, Nicolas Penel
BACKGROUND: In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit. METHODS: In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse...
March 10, 2017: Cancer
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#16
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28275743/regorafenib-lights-and-shadows-of-antiangiogenic-therapies-in-gastric-cancer
#17
COMMENT
Caterina Vivaldi, Alfredo Falcone, Lorenzo Fornaro
No abstract text is available yet for this article.
2017: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28259999/clinical-and-molecular-assessment-of-regorafenib-monotherapy
#18
Nao Kakizawa, Koichi Suzuki, Taro Fukui, Yuji Takayama, Kosuke Ichida, Yuta Muto, Fumi Hasegawa, Fumiaki Watanabe, Rina Kikugawa, Shingo Tsujinaka, Kazushige Futsuhara, Yasuyuki Miyakura, Hiroshi Noda, Toshiki Rikiyama
Regorafenib has shown survival benefits in metastatic colorectal cancer patients who were exacerbated after all standard therapies. Some patients, however, exhibit severe adverse events (AEs) resulting in treatment discontinuation. Therefore, the selection of patients likely to benefit from regorafenib is crucial. Twenty patients were treated with regorafenib for metastatic colorectal cancer; 122 plasma samples were taken from 16 of these patients for monitoring of circulating tumor DNA (ctDNA) in the blood...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259285/serum-and-tissue-markers-in-colorectal-cancer-state-of-art
#19
REVIEW
Massimiliano Berretta, Lara Alessandrini, Chiara De Divitiis, Guglielmo Nasti, Arben Lleshi, Raffaele Di Francia, Gaetano Facchini, Carla Cavaliere, Carlo Buonerba, Vincenzo Canzonieri
Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade, the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e. bevacizumab, cetuximab, panitumab, aflibercept and regorafenib), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Molecular studies have recently widened the opportunity for testing new possible markers, but actually, only few markers can be recommended for practical use in clinic...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28236743/direct-binding-of-microrna-21-pre-element-with-regorafenib-an-alternative-mechanism-for-anti-colorectal-cancer-chemotherapy
#20
Xiaobing Chen, Bojian Xie, Liang Cao, Feng Zhu, Beibei Chen, Huifang Lv, Xingxing Fan, Lili Han, Liangyu Bie, Xinguang Cao, Xiaokun Shen, Feilin Cao
The Regorafenib is a broad-spectrum kinase inhibitor that has been approved to treat colorectal cancer (CRC). However, evidences have shown that the agent is also implicated in drug interaction with microRNA-21 (miR-21), an oncogenic miRNA which plays a key role in resisting programmed cell death in CRC cells. Here, we supposed that, instead of kinase inhibition, Regorafenib can directly bind to and then stabilize miR-21 pre-element, thus preventing RNase Dicer-meditated cleavage of the pre-element to mature miR-21...
May 2017: Journal of Molecular Graphics & Modelling
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