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regorafenib

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https://www.readbyqxmd.com/read/29455269/the-efficacy-and-safety-of-targeted-therapy-with-or-without-chemotherapy-in-advanced-gastric-cancer-treatment-a-network-meta-analysis-of-well-designed-randomized-controlled-trials
#1
REVIEW
Ting-Ting Zhao, Hao Xu, Hui-Mian Xu, Zhen-Ning Wang, Ying-Ying Xu, Yong-Xi Song, Song-Cheng Yin, Xing-Yu Liu, Zhi-Feng Miao
BACKGROUND: Advanced gastric cancer (AGC) is a severe malignant tumor associated with high mortality. Targeted therapy is an important approach for improving the therapeutic effects of AGC treatment. This study evaluates the efficacy and safety of targeted agents for AGC patients. METHODS: PubMed, EmBase, and the Cochrane Library were searched for double-blind randomized controlled trials (RCTs) of AGC treatments published prior to July 2017. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and severe adverse effects (AEs) were evaluated to determine the efficacy and safety of targeted agents...
February 17, 2018: Gastric Cancer
https://www.readbyqxmd.com/read/29453759/systemic-treatment-of-patients-with-advanced-unresectable-hepatocellular-carcinoma-emergence-of-therapies
#2
REVIEW
Weijing Sun, Roniel Cabrera
To date, sorafenib, a multiple tyrosine kinase inhibitor, is the only systemic agent approved by the FDA in the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Several other tyrosine kinase-inhibiting agents have been investigated in the first-line setting, either alone (sunitinib, brivanib, linifanib, and lenvatinib) or in combination with sorafenib (erlotinib and doxorubicin) in phase 3 trials. However, none of these studies demonstrated an improvement in survival over sorafenib...
February 17, 2018: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29452346/beyond-second-line-therapy-in-patients-with-metastatic-colorectal-cancer-a-systematic-review
#3
D Arnold, G W Prager, A Quintela, A Stein, S Moreno, N Mounedji, J Taieb
Background: The optimal chemotherapeutic regimen for use beyond the second-line for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials and methods: We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC...
February 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29449894/personalization-of-regorafenib-treatment-in-metastatic-gastrointestinal-stromal-tumours-in-real-life-clinical-practice
#4
Margherita Nannini, Maria Concetta Nigro, Bruno Vincenzi, Elena Fumagalli, Giovanni Grignani, Lorenzo D'Ambrosio, Giuseppe Badalamenti, Lorena Incorvaia, Raffaella Bracci, Silvia Gasperoni, Maristella Saponara, Lidia Gatto, Valentina Indio, Annalisa Astolfi, Valerio Di Scioscio, Paolo G Casali, Giuseppe Tonini, Massimo Aglietta, Antonio Russo, Guido Biasco, Maria A Pantaleo
Background: Regorafenib (REG) has now been approved as the standard third-line therapy in metastatic gastrointestinal stromal tumour (GIST) patients at the recommended dose and schedule of 160 mg once daily for the first 3 weeks of each 4-week cycle. However, it has a relevant toxicity profile that mainly occurs within the first cycles of therapy, and dose and schedule adjustments are often required to reduce the frequency or severity of adverse events and to avoid early treatment discontinuation...
December 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29442015/prognostic-factors-in-patients-with-advanced-and-recurrent-colorectal-cancer-receiving-last-line-chemotherapy
#5
M Kimura, M Iwai, E Usami, H Teramachi, T Yoshimura
For patients with advanced/recurrent colorectal cancer, the trifluridine/tipiracil combination tablet (TAS 102) and regorafenib are last-line treatments. This study aimed to clarify prognostic factors in patients receiving last-line chemotherapy. Between April 2014 and December 2016, 47 patients received last-line chemotherapy at Ogaki Municipal Hospital, Japan. The primary outcome was overall survival. To determine factors associated with survival, those considered significant in the univariate analysis (p <0...
February 1, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29433345/computed-tomography-densitometric-study-of-anti-angiogenic-effect-of-regorafenib-in-colorectal-cancer-liver-metastasis
#6
Alfonso Reginelli, Alfredo Clemente, Claudia Cardone, Fabrizio Urraro, Andrea Izzo, Erika Martinelli, Teresa Troiani, Fortunato Ciardiello, Luca Brunese, Salvatore Cappabianca
AIM: Regorafenib induces radiological changes in liver metastasis among patients with metastatic colorectal cancer (mCRC). The standard criteria used to evaluate solid tumor response (Response Evaluation Criteria in Solid Tumors) may be limited in assessing response to biologic agents with anti-angiogenic action. PATIENTS & METHODS: A total of 67 hepatic lesions in 32 selected patients were analyzed to evaluate tumor attenuation as measured by Hounsfield unit (HU) and size changes...
February 13, 2018: Future Oncology
https://www.readbyqxmd.com/read/29423069/combined-effects-of-plk1-and-ras-in-hepatocellular-carcinoma-reveal-rigosertib-as-promising-novel-therapeutic-dual-hit-option
#7
Peter Dietrich, Kim Freese, Abdo Mahli, Wolfgang Erwin Thasler, Claus Hellerbrand, Anja Katrin Bosserhoff
Inhibition of RAS-RAF-ERK-signaling is a major mechanism mediated by the multi-kinase inhibitors sorafenib and regorafenib, the only effective therapeutic approaches for advanced hepatocellular carcinoma (HCC). This underlines the importance of RAS-RAF-ERK-signaling in HCC. Most RAS isoforms were not yet described to play crucial roles in HCC. However, several studies indicate that the HRAS isoform can function as potent oncogene in HCC, but pharmacologic RAS inhibition has not yet been investigated. Moreover, the cell cycle promoting polo-like kinase 1 (PLK1) is an increasingly recognized therapeutic target in HCC that can be activated by RAS-RAF-signaling...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29411249/multi-targeted-tyrosine-kinase-inhibitor-induced-hyperammonemic-encephalopathy-a-report-of-two-cases-using-pazopanib-sunitinib-and-regorafenib
#8
Noppadon Kongsuphon, Maturos Soukavanitch, Noramon Teeraaumpornpunt, Jitprapa Konmun, Touch Ativitavas, Nuttapong Ngamphaiboon
No abstract text is available yet for this article.
February 7, 2018: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29409752/activation-loop-targeting-strategy-for-design-of-receptor-interacting-protein-kinase-2-ripk2-inhibitors
#9
Chalada Suebsuwong, Daniel M Pinkas, Soumya S Ray, Joshua C Bufton, Bing Dai, Alex N Bullock, Alexei Degterev, Gregory D Cuny
Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pan-kinase inhibitor regorafenib that aim to engage basic activation loop residues Lys169 or Arg171...
January 31, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29402244/changes-in-ct-morphology-can-be-an-independent-response-marker-for-patients-receiving-regorafenib-for-colorectal-liver-metastases-retrospective-pilot-study
#10
Yukinori Ozaki, Junichi Shindoh, Wataru Gonoi, Yujiro Nishioka, Chihiro Kondoh, Yuko Tanabe, Shuichiro Matoba, Hiroya Kuroyanagi, Masaji Hashimoto, Toshimi Takano
BACKGROUND: Regorafenib is a multi-kinase inhibitor, which was shown to be effective for patients with metastatic colorectal cancer refractory to standard therapies. However, its patterns of response has not yet been fully understood. METHODS: Clinical records of 10 patients who received regorafenib for evaluable colorectal liver metastases were reviewed. Response to chemotherapy was evaluated with the RECIST and morphologic response criteria, and its clinical relevance was analyzed...
February 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29394758/-long-term-survival-of-a-patient-with-metastatic-liver-and-para-aortic-lymph-node-cancer-from-colon-cancer-treated-with-regorafenib
#11
Nobuyuki Watanabe, Shigenori Akagi, Hiroyuki Inoue, Hiroki Nakatsuji, Hiroshi Ito, Atsushi Toma, Kenji Nakamura, Toshiya Ochiai, Eigo Otsuji
A 54-year-old man was presented at our hospital with weight loss.He diagnosed with colorectal cancer, multiple liver metastases and para-aortic lymph node metastasis.After undergoing colostomy, he was treated sequentially with mFOLFOX6 plus bevacizumab(Bmab), FOLFIRI plus Bmab or Pmab, according to the guideline.Since these chemotherapy resulted in progressive disease, regorafenib was administered as a salvage-line treatment.PET -CT showed only para-aortic lymph node swelling with high FDG uptake.Severe adverse effects were developed shortly after regorafenib treatment so he requireda reduction in dose...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29387115/synthesis-and-characterization-of-some-novel-diaryl-urea-derivatives-bearing-quinoxalindione-moiety
#12
Sedighe Sadeghian-Rizi, Ghadamali Khodarahmi, Amirhossein Sakhteman, Ali Jahanian-Najafabadi, Mahboubeh Rostami, Mahmoud Mirzaei, Farshid Hassanzadeh
Diaryl urea derivatives have exhibited a broad spectrum of biochemical effects and pharmaceutical applications. Several diaryl urea derivatives such as sorafenib, regorafenib, linifanib, and tivozanib and lenvatinib are in clinical trial or clinical use. Therefore, development of small molecules within the diaryl urea scaffold with the ability of binding to variety of enzymes and receptors in the biological system are an interesting topic for researchers. Sorafenib as a diaryl urea derivative is a well-known anticancer agent...
February 2018: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29386313/benefit-risk-summary-of-regorafenib-for-the-treatment-of-patients-with-advanced-hepatocellular-carcinoma-that-has-progressed-on-sorafenib
#13
Lorraine Pelosof, Steven Lemery, Sandra Casak, Xiaoping Jiang, Lisa Rodriguez, Vadryn Pierre, Youwei Bi, Jiang Liu, Jeanne Fourie Zirkelbach, Anuja Patel, Kirsten B Goldberg, Amy E McKee, Patricia Keegan, Richard Pazdur
On April 27, 2017, the U.S. Food and Drug Administration approved regorafenib for the treatment of patients with advanced hepatocellular carcinoma (HCC) who had previously been treated with sorafenib. Approval was based on the results of a single, randomized, placebo-controlled trial (RESORCE) that demonstrated an improvement in overall survival (OS). Patients were randomly allocated to receive regorafenib160 mg orally once daily or matching placebo for the first 21 days of each 28-day cycle. The trial demonstrated a significant improvement in OS (hazard ratio [HR] = 0...
January 31, 2018: Oncologist
https://www.readbyqxmd.com/read/29376753/cardiovascular-diseases-in-patients-receiving-small-molecules-with-anti-vascular-endothelial-growth-factor-activity-a-meta-analysis-of-approximately-29-000-cancer-patients
#14
Matthias Totzeck, Raluca-Ileana Mincu, Simone Mrotzek, Dirk Schadendorf, Tienush Rassaf
Background Targeted therapy with tyrosine kinase inhibitors with anti-vascular endothelial growth factor activity improves survival of cancer patients. Cardiovascular complications are critical and it is unknown whether these require specific treatment strategies. We aimed to clarify the associated risk of cardiovascular adverse events in patients treated with tyrosine kinase inhibitors. Design The design of this study was a meta-analysis of randomised controlled trials. Methods We searched PubMed, Cochrane, EMBASE and Web of Science databases for randomised controlled trials published until January 2017 that assessed patients with different types of cancer treated with or without tyrosine kinase inhibitors in addition to standard chemotherapy...
January 1, 2018: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/29371921/identification-of-malt1-as-both-a-prognostic-factor-and-a-potential-therapeutic-target-of-regorafenib-in-cholangiocarcinoma-patients
#15
Chun-Nan Yeh, Yu-Chan Chang, Yeu Su, Dennis Shin-Shian Hsu, Chi-Tung Cheng, Ren-Chin Wu, Yi-Hsiu Chung, Kun-Chun Chiang, Ta-Sen Yeh, Meng-Lun Lu, Chun-Yu Liu, Peter Mu-Hsin Chang, Ming-Han Chen, Chi-Ying F Huang, Michael Hsiao, Ming-Huang Chen
Intrahepatic cholangiocarcinoma (CCA) is an aggressive cancer that lacks an effective targeted therapy. Here, we assessed the therapeutic efficacy of regorafenib in CCA, as well as elucidated its underlying mechanism. We first demonstrated that regorafenib not only inhibited growth but also induced apoptosis in human CCA cells. Subsequently, we used in silico approaches to identify MALT1 (Mucosa-associated lymphoid tissue protein 1), which plays an important role in activating NF-κB, as a potential target of regorafenib...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29362328/-treatment-of-regorafenib-in-patients-with-metastatic-or-unresectable-gastrointestinal-stromal-tumor-after-failure-of-imatinib-and-sunitinib
#16
Yurina Saito, Tsuyoshi Takahashi, Koji Tanaka, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichiro Doki
Imatinibmesylate has dramatically improved the survival with unresectable or metastatic GIST, whereas many patients subsequently develop imatinib resistance. Followed by sunitinib, regorafenib has been approved since 2013 in Japan. We aimed to assess efficacy and safety of regorafenibin GIST patients in clinical setting. The study was conducted between August 2013 and April 2016, among 11 patients with GIST treated by regorafenib. The median treatment duration was 8.4 months. The median progression-free survival(PFS)was 7...
January 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29360073/immunostimulatory-monoclonal-antibodies-for-hepatocellular-carcinoma-therapy-trends-and-perspectives
#17
Guillermo D Mazzolini, Mariana Malvicini
Hepatocellular carcinoma (HCC) is the second cause of cancer-related death in the world and is the main cause of death in cirrhotic patients. Unfortunately, the incidence of HCC has grown significantly in the last decade. Curative treatments such as surgery, liver transplantation or percutaneous ablation can only be applied in less than 30% of cases. The multikinase inhibitor sorafenib is the first line therapy for advanced HCC. Regorafenib is the standard of care for second-line patients. However, novel and more specific potent therapeutic approaches for advanced HCC are still needed...
2018: Medicina
https://www.readbyqxmd.com/read/29359239/the-orally-available-multikinase-inhibitor-regorafenib-bay-73-4506-in-multiple-myeloma
#18
Iris Breitkreutz, Klaus Podar, Vianihuini Figueroa-Vazquez, Scott Wilhelm, Patrick J Hayden, Kenneth C Anderson, Marc S Raab
A promising approach to the treatment of multiple myeloma (MM) involves agents that target not only the myeloma cells directly, but also the tumor microenvironment which promotes tumor cell growth, angiogenesis, and MM bone disease. Here we investigate the orally available multikinase inhibitor, regorafenib (BAY 73-4506), for its therapeutic efficacy in MM. Regorafenib is a potent inhibitor of angiogenic (VEGFR 1-3, PDGFR-b) as well as oncogenic (c-KIT, RET, FGFR, Raf) kinases. We show that regorafenib induces apoptosis in all MM cell lines at below clinically achievable concentrations...
January 23, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29341879/mechanisms-of-mitochondrial-toxicity-of-the-kinase-inhibitors-ponatinib-regorafenib-and-sorafenib-in-human-hepatic-hepg2-cells
#19
Franziska Paech, Cécile Mingard, David Grünig, Vanessa F Abegg, Jamal Bouitbir, Stephan Krähenbühl
Previous studies have shown that certain kinase inhibitors are mitochondrial toxicants. In the current investigation, we determined the mechanisms of mitochondrial impairment by the kinase inhibitors ponatinib, regorafenib, and sorafenib in more detail. In HepG2 cells cultured in galactose and exposed for 24 hours, all three kinase inhibitors investigated depleted the cellular ATP pools at lower concentrations than cytotoxicity occurred, compatible with mitochondrial toxicity. The kinase inhibitors impaired the activity of different complexes of the respiratory chain in HepG2 cells exposed to the toxicants for 24 hours and in isolated mouse liver mitochondria exposed acutely...
January 13, 2018: Toxicology
https://www.readbyqxmd.com/read/29334307/regorafenib-regresses-an-imatinib-resistant-recurrent-gastrointestinal-stromal-tumor-gist-with-a-mutation-in-exons-11-and-17-in-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#20
Kentaro Miyake, Kei Kawaguchi, Tasuku Kiyuna, Masuyo Miyake, Kentaro Igarashi, Zhiying Zhang, Takashi Murakami, Yunfeng Li, Scott D Nelson, Irmina Elliott, Tara Russell, Arun Singh, Yukihiko Hiroshima, Masashi Momiyama, Ryusei Matsuyama, Takashi Chisima, Itaru Endo, Fritz C Eilber, Robert M Hoffman
Gastrointestinal stromal tumor (GIST) is a rare type of sarcoma. The aim of this study was to determine drug sensitivity for a regionally-recurrent case of GIST using a patient-derived orthotopic xenograft (PDOX) model. The PDOX model was established in the anterior wall of the stomach. GIST PDOX models were randomized into 5 groups of 6 mice each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group (oral administration (p.o.), daily, for 3 weeks); G3, sunitinib group (p.o., daily, for 3 weeks); G4, regorafenib (p...
January 15, 2018: Cell Cycle
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