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https://www.readbyqxmd.com/read/28522682/regorafenib-approved-for-liver-cancer
#1
(no author information available yet)
The FDA recently expanded label indications for regorafenib to include treating patients with advanced hepatocellular carcinoma whose disease has progressed on the standard of care, sorafenib. Until now, these patients have had no other treatment options. Regorafenib is the first drug to be approved for liver cancer in a decade.
May 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28520456/development-and-validation-of-a-micellar-liquid-chromatographic-method-to-determine-three-antitumorals-in-plasma
#2
Josep Esteve Romero, Jaume Albiol Chiva, Juan Peris-Vicente, Enrique Ochoa-Aranda
AIM: A micellar liquid chromatographic method to determine several anticancer drugs (pazopanib, dabrafenib and regorafenib) in plasma was developed and validated by the guidelines of the EMA. EXPERIMENTAL: Plasma samples were directly injected, after a 1/5-dilution in a micellar solution. The drugs were resolved in <18 min using a C18 column. The mobile phase was an aqueous solution of 0.12 M SDS - 2% 1-pentanol, buffered at pH 7. The detection was performed by absorbance at 260 nm...
May 18, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28509806/advances-in-management-of-hepatocellular-carcinoma
#3
Manon Allaire, Jean-Charles Nault
PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is one of the leading causes of death by cancer worldwide due to a dismal prognosis. The aim of this review is to summarize the main advances in the pathophysiology and management of HCC. RECENT FINDINGS: Genomic analysis has recently delineated the key signaling pathways aberrantly deregulated in HCC (telomere maintenance, cell cycle gene, Wnt/β-catenin, epigenetic modifier, oxidative stress etc.). Major advances in the clinical care of patients with HCC are helping to refine the diagnosis algorithm and tumor staging...
May 15, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28506080/hepatocellular-carcinoma-treatment-a-comparative-review-of-emerging-growth-factor-receptor-antagonists
#4
Su Jin Lee, Ho Yeong Lim
Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Over the last decade, sorafenib has been the only available therapeutic option for advanced HCC, although regorafenib recently showed a survival benefit compared with placebo in a second-line setting. Areas covered: This review discusses key published and ongoing studies with targeted agents in HCC, molecular targets of HCC, the mechanism of resistance to sorafenib, and the role of biomarker-enriched clinical trials. Expert opinion: The multiplicity of drivers and the existence of substantial molecular heterogeneity limit the benefits of targeted therapies in HCC...
May 16, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28494338/simultaneous-analysis-of-regorafenib-and-sorafenib-and-three-of-their-metabolites-in-human-plasma-using-lc-ms-ms
#5
Marie Allard, Nihel Khoudour, Benoît Rousseau, Charlotte Joly, Charlotte Costentin, Benoît Blanchet, Christophe Tournigand, Anne Hulin
A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, performed by electrospray ionization in positive mode using a triple quadrupole mass spectrometry, has been developed and validated for the simultaneous determination of regorafenib (REGO), its two metabolites regorafenib-M2 and regorafenib-M5, sorafenib (SORA), and its N-oxide metabolite in human plasma. Separation is achieved on an Hypersil Gold(®) column using a gradient elution of 10mM ammonium formate containing 0.1% formic acid (A) and acetonitrile containing 0...
May 1, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28489887/regorafenib-inhibited-gastric-cancer-cells-growth-and-invasion-via-cxcr4-activated-wnt-pathway
#6
Xiao-Lin Lin, Qi Xu, Lei Tang, Li Sun, Ting Han, Li-Wei Wang, Xiu-Ying Xiao
AIM: Regorafenib is an oral small-molecule multi kinase inhibitor. Recently, several clinical trials have revealed that regorafenib has an anti-tumor activity in gastric cancer. However, only part of patients benefit from regorafenib, and the mechanisms of regorafenib's anti-tumor effect need further demonstrating. In this study, we would assess the potential anti-tumor effects and the underlying mechanisms of regorafenib in gastric cancer cells, and explore novel biomarkers for patients selecting of regorafenib...
2017: PloS One
https://www.readbyqxmd.com/read/28487491/a-phase-ii-trial-of-regorafenib-in-patients-with-metastatic-and-or-a-unresectable-gastrointestinal-stromal-tumor-harboring-secondary-mutations-of-exon-17
#7
Chun-Nan Yeh, Ming-Huang Chen, Yen-Yang Chen, Ching-Yao Yang, Chueh-Chuan Yen, Chin-Yuan Tzen, Li-Tzong Chen, Ji-Shi Chen
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are caused by the constitutive activation of KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations. Imatinib selectively inhibits KIT and PDGFR, leading to disease control for 80%-90% of patients with metastatic GIST. Imatinib resistance can occur within a median of 2-3 years due to secondary mutations in KIT. According to preclinical studies, both imatinib and sunitinib are ineffective against exon 17 mutations. However, the treatment efficacy of regorafenib for patients with GIST with exon 17 mutations is still unknown...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28482674/management-of-hepatocellular-in-the-united-states
#8
Ali A Mokdad, Caitlin A Hester, Amit G Singal, Adam C Yopp
Hepatocellular carcinoma (HCC) is a major cause of cancer burden globally. In the United States, the incidence of HCC is forecast to continue to rise for the next 15 years. Patients with HCC vary markedly owing to heterogeneous tumor characteristics and concomitant liver dysfunction. In the United States and Europe, HCC is staged and managed according to the Barcelona Clinic Liver Cancer (BCLC) system. For very early and early stage HCC, or BCLC 0/A, liver transplant is the optimal treatment option. Liver resection and radiofrequency or microwave ablation are alternative treatment options...
April 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28480064/systemic-therapy-for-advanced-hepatocellular-carcinoma-an-update
#9
REVIEW
Jasmin Radhika Desai, Sebastian Ochoa, Petra Alexandra Prins, Aiwu Ruth He
Advanced hepatocellular carcinoma (HCC) is a deadly disease with few systemic therapeutic options. Sorafenib is the only agent to be FDA approved for the first-line treatment of patients with HCC. This drug increases overall survival (OS) by 3 months compared with placebo (10.7 months with sorafenib vs. 7.7 months with placebo). More recently, the RESORCE trial demonstrated efficacy of regorafenib in the second-line treatment of HCC: OS was increased from 7.8 months with placebo to 10.6 months with regorafenib after patients experienced disease progression on sorafenib...
April 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28480062/locoregional-and-systemic-therapy-for-hepatocellular-carcinoma
#10
REVIEW
Olumide B Gbolahan, Michael A Schacht, Eric W Beckley, Thomas P LaRoche, Bert H O'Neil, Maximilian Pyko
The management of hepatocellular carcinoma (HCC) remains challenging due to late presentation and the presence of accompanying liver dysfunction. As such, most patients are not eligible for curative resection and liver transplant. Management in this scenario depends on a number of factors including hepatic function, tumor burden, patency of hepatic vasculature and patients' functional status. Based on these, patients can be offered catheter based intra-arterial therapy for intermediate stage disease and in more advanced disease, sorafenib...
April 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28479358/involvement-of-the-transporters-p-gp-and-bcrp-in-dermal-distribution-of-the-multi-kinase-inhibitor-regorafenib-and-its-active-metabolites
#11
Ken-Ichi Fujita, Yusuke Masuo, Erina Yamazaki, Toshiki Shibutani, Yutaro Kubota, Noritaka Nakamichi, Yasutsuna Sasaki, Yukio Kato
Regorafenib is a multi-kinase inhibitor orally administered to colorectal cancer patients, and is known to often exhibit dermal toxicity. The purpose of the present study was to clarify possible involvement of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in the dermal accumulation of regorafenib and its active metabolites M-2 and M-5. Following intravenous administration in Abcb1a/1b/bcrp(-/-) (TKO) and wild-type (WT) mice, delayed plasma clearance of M-2 and M-5, but not regorafenib, was observed in TKO mice compared to WT mice...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28468766/regorafenib-induced-hypothyroidism-and-cancer-related-fatigue-is-there-a-potential-link
#12
Fabiana Pani, Matteo Massidda, Valeria Pusceddu, Marco Puzzoni, Elena Massa, Clelia Madeddu, Mario Scartozzi, Stefano Mariotti
OBJECTIVE: Thyroid dysfunction has been reported during Regorafenib (Reg) administration, but no detailed study is presently available. DESIGN: Prospective, observational cohort study. Patients with documented metastatic colorectal cancer and progression of disease during or within 3 months after the last standard therapy, with no evidence and history of previous thyroid disease were enrolled. METHODS: Twenty-five consecutive patients were evaluated before and 8-50 weeks after initiating Reg therapy by monthly clinical, ultrasound and laboratory (thyrotropin [TSH], free thyroxine [fT4], antithyroglobulin [TgAb] and antithyroid peroxidase [TPOAb]) evaluation...
May 3, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28454726/predictive-value-of-early-tumor-shrinkage-and-density-reduction-of-lung-metastases-in-patients-with-metastatic-colorectal-cancer-treated-with-regorafenib
#13
Hannes Vanwynsberghe, Xander Verbeke, Johan Coolen, Eric Van Cutsem
INTRODUCTION: The benefit of regorafenib in colorectal cancer is not very pronounced. At present, there is lack of predictive biological or radiological markers. We studied if density reduction or small changes in size of lung metastases could be a predictive marker. METHODS: We retrospectively measured density in size of lung metastases of all patients included in the CORRECT and CONSIGN trials at our center. Contrast-enhanced CT scan at baseline and at week 8 were compared...
March 29, 2017: Clinical Colorectal Cancer
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
#14
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/28451414/response-to-regorafenib-at-an-initial-dose-of-120-mg-as-salvage-therapy-for-metastatic-colorectal-cancer
#15
Hiroshi Osawa
Regorafenib (Reg) is an oral multikinase inhibitor that has achieved improved overall survival in patients with metastatic colorectal cancer (mCRC) in the salvage therapy setting. However, Reg is difficult to manage and determine the optimal dose due to adverse events (AEs). The objective of this study was to retrospectively evaluate the clinical benefit and determine the optimal dose of Reg in mCRC patients. A total of 20 mCRC patients were enrolled in this retrospective study. Initially, 8 patients who received a starting dose of 160 mg Reg (160 mg group) once a day were evaluated; however, they were unable to continue with the initial dose of 160 mg due to grade 3 adverse events (AEs), such as hand-foot skin reaction (HFSR) and small intestinal hemorrhage...
March 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28450818/the-role-of-regorafenib-in-hepatocellular-carcinoma
#16
Catherine T Frenette
No abstract text is available yet for this article.
February 2017: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#17
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
#18
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
#19
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
#20
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)
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