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https://www.readbyqxmd.com/read/28089507/gastrointestinal-perforation-and-fistula-formation-in-5-patients-with-colorectal-cancer-during-treatment-with-regorafenib
#1
Ayako Doi, Yasutoshi Kuboki, Kohei Shitara, Shota Fukuoka, Hideaki Bando, Wataru Okamoto, Takashi Kojima, Toshihiko Doi, Atsushi Ohtsu, Takayuki Yoshino
No abstract text is available yet for this article.
December 28, 2016: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28065859/inhibition-of-human-udp-glucuronosyltransferase-enzymes-by-lapatinib-pazopanib-regorafenib-and-sorafenib-implications-for-hyperbilirubinemia
#2
John O Miners, Nuy Chau, Andrew Rowland, Kushari Burns, Ross A McKinnon, Peter I Mackenzie, Geoffrey T Tucker, Kathleen M Knights, Ganessan Kichenadasse
Kinase inhibitors (KIs) are a rapidly expanding class of drugs used primarily for the treatment of cancer. Data relating to the inhibition of UDP-glucuronosyltransferase (UGT) enzymes by KIs is sparse. However, lapatinib (LAP), pazopanib (PAZ), regorafenib (REG) and sorafenib (SOR) have been implicated in the development of hyperbilirubinemia in patients. This study aimed to characterise the role of UGT1A1 inhibition in hyperbilirubinemia and assess the broader potential of these drugs to perpetrate drug-drug interactions arising from UGT enzyme inhibition...
January 5, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28060884/contrast-enhanced-ultrasound-with-vegfr2-targeted-microbubbles-for-monitoring-regorafenib-therapy-effects-in-experimental-colorectal-adenocarcinomas-in-rats-with-dce-mri-and-immunohistochemical-validation
#3
Ralf Stefan Eschbach, Dirk-Andre Clevert, Heidrun Hirner-Eppeneder, Michael Ingrisch, Matthias Moser, Jessica Schuster, Dina Tadros, Moritz Schneider, Philipp Maximilian Kazmierczak, Maximilian Reiser, Clemens C Cyran
OBJECTIVES: To investigate contrast-enhanced ultrasound (CEUS) with VEGFR2-targeted microbubbles for monitoring therapy effects of regorafenib on experimental colon carcinomas in rats with correlation to dynamic contrast-enhanced MRI (DCE-MRI) and immunohistochemistry. MATERIALS AND METHODS: Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 21 (n = 11 therapy group; n = 10 control group) female athymic nude rats (Hsd: RH-Foxn1rnu)...
2017: PloS One
https://www.readbyqxmd.com/read/28052652/anti-angiogenic-therapy-in-patients-with-advanced-gastric-and-gastroesophageal-junction-cancer-a-systematic-review
#4
Li-Tzong Chen, Do-Youn Oh, Min-Hee Ryu, Kun-Huei Yeh, Winnie Yeo, Roberto Carlesi, Rebecca Cheng, Jongseok Kim, Mauro Orlando, Yoon-Koo Kang
Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress...
January 3, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28032528/chemotherapy-rechallenge-after-regorafenib-treatment-in-metastatic-colorectal-cancer-still-hope-after-the-last-hope
#5
Paola Bertocchi, Francesca Aroldi, Tiziana Prochilo, Fausto Meriggi, Giordano Domenico Beretta, Alberto Zaniboni
INTRODUCTION: The introduction of biological agents in cancer therapy is changing the progression of metastatic colorectal cancer. Currently, resistance to biological agents is an emerging problem; the progression of the disease is caused by the development of resistant clones. According to some authors, these clones can be re-sensitized to traditional and previously utilized chemotherapy agents. The results of the CORRECT study demonstrated the efficacy of regorafenib monotherapy in both KRAS wild type and mutant pretreated patients (pts)...
December 29, 2016: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28032146/effects-of-31-fda-approved-small-molecule-kinase-inhibitors-on-isolated-rat-liver-mitochondria
#6
Jun Zhang, Alec Salminen, Xi Yang, Yong Luo, Qiangen Wu, Matthew White, James Greenhaw, Lijun Ren, Matthew Bryant, William Salminen, Thomas Papoian, William Mattes, Qiang Shi
The FDA has approved 31 small-molecule kinase inhibitors (KIs) for human use as of November 2016, with six having black box warnings for hepatotoxicity (BBW-H) in product labeling. The precise mechanisms and risk factors for KI-induced hepatotoxicity are poorly understood. Here, the 31 KIs were tested in isolated rat liver mitochondria, an in vitro system recently proposed to be a useful tool to predict drug-induced hepatotoxicity in humans. The KIs were incubated with mitochondria or submitochondrial particles at concentrations ranging from therapeutic maximal blood concentrations (Cmax) levels to 100-fold Cmax levels...
December 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/28025473/-target-therapy-in-unresectable-or-metastatic-colorectal-cancer
#7
REVIEW
Jae Hyun Kim, Seun Ja Park
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Korea. Despite recent developments in the treatment of CRC, the median overall survival time in patients with metastatic CRC is less than 30 months. The biologic agents that target the epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have proven clinical benefits in the treatment of patient with metastatic CRC. Anti-EGFR agents, including cetuximab and panitumumab, as well as anti-VEGF agents, including bevacizumab, aflibercept, ramucirumab, and regorafenib have been shown to extend survival in combination with cytotoxic chemotherapy...
December 25, 2016: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28008149/idelalisib-induces-puma-dependent-apoptosis-in-colon-cancer-cells
#8
Shida Yang, Zhiyong Zhu, Xiaobing Zhang, Ning Zhang, Zhicheng Yao
Idelalisib, a PI3K inhibitor, specifically targeting p110δ, has been approved for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. However, the mechanisms of action of idelalisib in colon cancer cells are not well understood. We investigated how idelalisib suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. In this study, we found that idelalisib treatment induces PUMA in colon cancer cells irrespective of p53 status through the p65 pathway following AKT inhibition and glycogen synthase kinase 3β (GSK3β) activation...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28000898/regorafenib-induces-extrinsic-and-intrinsic-apoptosis-through-inhibition-of-erk-nf-%C3%AE%C2%BAb-activation-in-hepatocellular-carcinoma-cells
#9
Jai-Jen Tsai, Po-Jung Pan, Fei-Ting Hsu
The aim of the present study was to investigate the role of NF-κB inactivation in regorafenib-induced apoptosis in human hepatocellular carcinoma SK-HEP-1 cells. SK-HEP-1 cells were treated with different concentrations of the NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine (QNZ) or regorafenib for different periods. The effects of QNZ and regorafenib on cell viability, expression of NF-κB-modulated anti-apoptotic proteins and apoptotic pathways were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, DNA gel electrophoresis, flow cytometry and NF-κB reporter gene assay...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27995948/liver-cancer-regorafenib-a-new-resorce-in-hcc
#10
David Killock
No abstract text is available yet for this article.
December 20, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27972562/cost-effectiveness-analysis-of-regorafenib-in-gastrointestinal-stromal-tumours-in-england-using-crossover-adjustment-methods
#11
A Pitcher, E Grabbi, M Madin-Warburton, S Vadgama
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27972442/budget-impact-analysis-of-regorafenib-for-the-treatment-in-third-and-fourth-lines-of-metastasic-colorectal-cancer-in-spain
#12
E González Flores, R Vera García, E Sabater Cabrera, E Tirado Mercier, M Granell Villalon
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27938508/regorafenib-plus-folfiri-with-irinotecan-dose-escalated-according-to-uridine-diphosphate-glucuronosyltransferase-1a1-genotyping-in-patients-with-metastatic-colorectal-cancer
#13
Cheng-Jen Ma, Ching-Wen Huang, Yung-Sung Yeh, Hsiang-Lin Tsai, Huang-Ming Hu, I-Chen Wu, Tian-Lu Cheng, Jaw-Yuan Wang
We analyzed the results of previously treated patients with metastatic colorectal cancer (mCRC) who received regorafenib plus FOLFIRI with the irinotecan dose escalation on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping. Thirteen patients with previously treated mCRC were subjected to UGT1A1 genotyping between Oct 2013 and June 2015 and were administered regorafenib plus FOLFIRI with irinotecan dose escalation. Patients with UGT1A1*1/*1 and *1/*28 genotypes were administered 180 mg/m(2) 48 of irinotecan, whereas those with the UGT1A1*28/*28 genotype were administered 120 mg/m(2) 49 of irinotecan...
17, 2016: Oncology Research
https://www.readbyqxmd.com/read/27932229/regorafenib-for-patients-with-hepatocellular-carcinoma-who-progressed-on-sorafenib-treatment-resorce-a-randomised-double-blind-placebo-controlled-phase-3-trial
#14
Jordi Bruix, Shukui Qin, Philippe Merle, Alessandro Granito, Yi-Hsiang Huang, György Bodoky, Marc Pracht, Osamu Yokosuka, Olivier Rosmorduc, Valeriy Breder, René Gerolami, Gianluca Masi, Paul J Ross, Tianqiang Song, Jean-Pierre Bronowicki, Isabelle Ollivier-Hourmand, Masatoshi Kudo, Ann-Lii Cheng, Josep M Llovet, Richard S Finn, Marie-Aude LeBerre, Annette Baumhauer, Gerold Meinhardt, Guohong Han
BACKGROUND: There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. METHODS: In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled...
December 5, 2016: Lancet
https://www.readbyqxmd.com/read/27916795/first-and-second-line-targeted-systemic-therapy-in-hepatocellular-carcinoma-an-update-on-patient-selection-and-response-evaluation
#15
REVIEW
Johann von Felden, Kornelius Schulze, Ines Gil-Ibanez, Tobias Werner, Henning Wege
Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy...
November 28, 2016: Diagnostics
https://www.readbyqxmd.com/read/27906677/the-implication-of-flt3-amplification-for-flt-targeted-therapeutics-in-solid-tumors
#16
Sung Hee Lim, Sun-Young Kim, Kyung Kim, Hyojin Jang, Soomin Ahn, Kyoung-Mee Kim, Nayoung K D Kim, Woongyang Park, Su Jin Lee, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Young Suk Park, Se-Hoon Lee, Ho Yeong Lim, Keunchil Park, Won Ki Kang, Jeeyun Lee
We investigated the patients with solid cancers harboring Fms-like tyrosine kinase 3 (FLT3) amplification using targeted sequencing of tumor tissue specimen and FISH assay. Simultaneously, FLT3-amplified patient-derived cells (PDCs) were generated to evaluate the sensitivity to FLT3 inhibition. A patient with metastatic colon cancer who was previously treated with more than 3rd line cytotoxic chemotherapy was found to have FLT3 amplification and then received regorafenib showing partial response. In two PDC cell lines with FLT3 amplification, FLT3 mRNA expression was increased, however, the growth of tumor cells was not significantly inhibited by either regorafenib or sorafenib which is known to block the activity FLT3...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900102/comparison-of-cost-effectiveness-of-regorafenib-and-trifluridine-tipiracil-combination-tablet-for-treating-advanced-and-recurrent-colorectal-cancer
#17
Michio Kimura, Eiseki Usami, Mina Iwai, Makiko Go, Hitomi Teramachi, Tomoaki Yoshimura
Regorafenib and trifluridine/tipiracil combination tablet regimens are standard third-line or later treatments for advanced and recurrent colorectal cancer with no significant difference in efficacy. The present study aimed to compare the cost-effectiveness of using regorafenib vs. the trifluridine/tipiracil combination tablet. The expected cost was calculated based on data from patients with advanced and recurrent colorectal cancer who were treated with regorafenib or trifluridine/tipiracil combination tablet...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27888325/total-lesion-glycolysis-tlg-as-an-imaging-biomarker-in-metastatic-colorectal-cancer-patients-treated-with-regorafenib
#18
Yoojoo Lim, Ji-In Bang, Sae-Won Han, Jin Chul Paeng, Kyung-Hun Lee, Jee Hyun Kim, Gyeong Hoon Kang, Seung-Yong Jeong, Kyu Joo Park, Tae-You Kim
PURPOSE: This study was performed to evaluate whether fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) could predict treatment outcome of regorafenib in metastatic colorectal cancer (mCRC). METHODS: Previously treated refractory mCRC patients were enrolled into a prospective biomarker study of regorafenib. For this sub-study, the results of FDG PET/CT scans at baseline and after two cycles of treatment were analyzed. Various metabolic parameters obtained from PET images were analyzed in relation to treatment outcome...
November 25, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27865140/overcoming-dynamic-molecular-heterogeneity-in-metastatic-colorectal-cancer-multikinase-inhibition-with-regorafenib-and-the-case-of-rechallenge-with-anti-egfr
#19
REVIEW
Andrea Sartore-Bianchi, Salvatore Siena, Giuseppe Tonini, Alberto Bardelli, Daniele Santini
In metastatic colorectal cancer (mCRC), fluorouracil-based combination therapy with oxaliplatin or irinotecan is the mainstay of first-line treatment. Patient survival has been significantly improved with the introduction of monoclonal antibodies against VEGF (bevacizumab), VEGFR2 (ramucirumab) or EGFR (cetuximab or panitumumab) in first- and second-line therapies. However, all patients treated with chemotherapy and targeted therapies will eventually relapse, and recently the emergence of alterations in EGFR, RAS, BRAF, ERB-B2, MET and possibly in other genes has been shown to jeopardize response to EGFR blockade...
December 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27864220/estimating-12-weeks-death-probability-in-patients-with-refractory-metastatic-colorectal-cancer-the-colon-life-nomogram
#20
F Pietrantonio, R Miceli, L Rimassa, S Lonardi, G Aprile, A Mennitto, F Marmorino, S Bozzarelli, L Antonuzzo, E Tamburini, F Morano, D Rossini, F Battaglin, M Baretti, R Berenato, V Formica, S Mosconi, F Petrelli, M Ghidini, F Loupakis, D Spada, S Cinieri, G Beretta, A Falcone, F de Braud, C Cremolini
BACKGROUND: Regorafenib and TAS-102 have recently demonstrated statistically significant survival gains in patients with refractory metastatic colorectal cancer (mCRC). Life expectancy ≥12 weeks was an inclusion criterion in registrative trials, and the identification of proper clinical selection tools for the daily use of these drugs in heavily pre-treated patients is needed to improve the cost-benefit ratio. We aimed at building a nomogram able to predict death probability within 12 weeks from the date of assessment of refractory mCRC...
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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