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https://www.readbyqxmd.com/read/29905927/multicenter-randomized-double-blind-phase-2-trial-of-folfiri-with-regorafenib-or-placebo-as-second-line-therapy-for-metastatic-colorectal-cancer
#1
Hanna K Sanoff, Richard M Goldberg, Anastasia Ivanova, Seamus O'Reilly, Samer S Kasbari, Richard D Kim, Ray McDermott, Dominic T Moore, William Zamboni, William Grogan, Allen Lee Cohn, Tanios S Bekaii-Saab, Gregory Leonard, Theresa Ryan, Olugbenga O Olowokure, Nishan H Fernando, John McCaffrey, Bassel F El-Rayes, Anne M Horgan, Gary Bradley Sherrill, George Hosni Yacoub, Bert H O'Neil
BACKGROUND: Regorafenib, a multikinase inhibitor that inhibits angiogenesis, growth, and proliferation, prolongs survival as monotherapy in patients with refractory colorectal cancer. This international, double-blind, placebo-controlled, multicenter trial assessed the efficacy of regorafenib with folinic acid, fluorouracil, and irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer who progressed on first-line oxaliplatin and fluoropyrimidine enrolled at 45 sites in the United States and Ireland...
June 15, 2018: Cancer
https://www.readbyqxmd.com/read/29902612/efficacy-and-safety-of-regorafenib-compared-to-placebo-and-to-post-cross-over-regorafenib-in-advanced-non-adipocytic-soft-tissue-sarcoma
#2
Thomas Brodowicz, Olivier Mir, Jennifer Wallet, Antoine Italiano, Jean-Yves Blay, François Bertucci, Wolfgang Eisterer, Christine Chevreau, Sophie Piperno-Neumann, Emmanuelle Bompas, Thomas Ryckewaert, Bernadette Liegl-Antzwager, Julien Thery, Nicolas Penel, Axel Le Cesne, Marie-Cécile Le Deley
INTRODUCTION: The placebo-controlled phase-2 REGOSARC trial demonstrated the efficacy of regorafenib in patients with leiomyosarcoma, synovial sarcoma and other non-adipocytic sarcoma but not in liposarcoma. Patients initially allocated to placebo were allowed to receive regorafenib after progression. We report here an updated analysis of the trial including evaluation of regorafenib activity after cross-over. METHODS: From June 2013 to December 2014, 139 patients were enrolled in the non-adipocytic sarcoma cohorts...
June 11, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29888133/shift-in-vegfa-isoform-balance-towards-more-angiogenic-variants-is-associated-with-tumor-stage-and-differentiation-of-human-hepatocellular-carcinoma
#3
Mikhail S Chesnokov, Polina A Khesina, Darya A Shavochkina, Inna F Kustova, Leonid M Dyakov, Olga V Morozova, Nikolai S Mugue, Nikolay E Kudashkin, Ekaterina A Moroz, Yuri I Patyutko, Natalia L Lazarevich
Background: Hepatocellular carcinoma (HCC) is the most common and aggressive type of malignant liver tumor. HCC progression depends significantly on its vascularization and formation of new blood vessels. Vascular endothelial growth factor A (VEGFA) is a crucial regulator of tumor vascularization and components of VEGF-induced cell signaling pathways are important targets of therapeutical drugs that demonstrated the highest efficiency in case of advanced HCC (sorafenib and regorafenib)...
2018: PeerJ
https://www.readbyqxmd.com/read/29885413/efficacy-of-annexin-a3-blockade-in-sensitizing-hepatocellular-carcinoma-to-sorafenib-and-regorafenib
#4
Man Tong, Noélia Che, Lei Zhou, Steve T Luk, Phillis W Kau, Stella Chai, Elly S Ngan, Chung-Mau Lo, Kwan Man, Jin Ding, Terence K Lee, Stephanie Ma
BACKGROUND & AIMS: Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Sorafenib is the only FDA approved first-line targeted drug for advanced HCC, but its effect on patients' survival gain is limited. Further, patients ultimately present disease progression. A better understanding of causes of sorafenib resistance, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCC...
June 6, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29868467/advances-and-challenges-on-management-of-gastrointestinal-stromal-tumors
#5
REVIEW
Lin Mei, Wei Du, Michael Idowu, Margaret von Mehren, Sosipatros A Boikos
Gastrointestinal stromal tumors (GISTs) originate from interstitial cells of Cajal and account for over 5,000 newly diagnosed cases in the United States. The discovery of activated KIT and PDGFRA mutations and introduction of imatinib revolutionized the treatment strategy and opened up the new era of target therapy for solid tumors. Although surgery remains the primary modality of treatment for curative purpose, almost half of the patients experienced disease recurrence. Tailoring (neo)-adjuvant treatment with imatinib is ongoing to meet the need for an effective therapy...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29845710/analysis-of-the-liver-functional-reserve-of-patients-with-advanced-hepatocellular-carcinoma-undergoing-sorafenib-treatment-prospects-for-regorafenib-therapy
#6
Takeshi Terashima, Tatsuya Yamashita, Hajime Sunagozaka, Kuniaki Arai, Kazunori Kawaguchi, Kazuya Kitamura, Taro Yamashita, Yoshio Sakai, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko
AIM: This study aimed to investigate liver functional reserves during sorafenib treatment for advanced hepatocellular carcinoma (HCC), to identify predictive factors for maintaining them, and to analyze the proportion of the candidate for regorafenib which have proven to improve patients outcome in RESORCE trial. METHODS: We retrospectively investigated Child-Pugh scores during and after sorafenib treatment and evaluated their effects on second-line treatment and outcomes of 125 patients with advanced HCC...
May 29, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29807383/-hepatocellular-carcinoma-new-multimodal-therapy-concepts
#7
Michael Schultheiß, Dominik Bettinger, Stefan Fichtner-Feigl, Robert Thimme
STATUS QUO:  Hepatocellular carcinoma guidelines are currently under revision. A new edition is expected in 2018. Patients with chronic liver diseases or cirrhosis require HCC screening by ultrasound every 6 months. Surgical resection or liver transplantation are curative treatment options for early stage HCC. LOCOREGIONAL THERAPY APPROACHES:  A more and more common and well tolerated locoregional therapy approach based on study data is selective internal radio therapy (SIRT), although studies did not show an improvement in outcome comparing SIRT to transarterial chemotherapy (TACE) in BCLC B or sorafenib in BCLC C...
June 2018: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29803964/in-silico-in-vitro-discovery-of-untargeted-kinase-inhibitor-interactions-from-kinase-targeted-therapies-a-case-study-on-the-cancer-mapk-signaling-pathway
#8
Li Meng, Zhijun Huang
Protein kinase inhibitors have been widely used as therapeutic agents to treat a variety of diseases, but many of them may cause off-target effects by unexpectedly targeting other noncognate kinases due to high conversion across the protein kinase family. The mitogen-activated protein kinase (MAPK) signaling pathway plays an essential role in tumorigenesis, which has been recognized as a high priority in the druggable target candidates of anticancer therapy. Here, we attempt to investigate the untargeted kinase-inhibitor interactions (UKIIs) of kinase-targeted therapies for the cancer MAPK signaling cascade via an integration of biomolecular modeling, cell viability assay and kinase inhibition analysis...
May 17, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29803544/real-world-treatment-patterns-among-patients-with-colorectal-cancer-treated-with-trifluridine-tipiracil-and-regorafenib
#9
Anuj K Patel, Mei S Duh, Victoria Barghout, Mihran A Yenikomshian, Yongling Xiao, Willy Wynant, Majid Tabesh, Charles S Fuchs
BACKGROUND: Trifluridine/tipiracil (FTD/TPI) and regorafenib (REG) prolong survival in refractory metastatic colorectal cancer (mCRC) and have similar indications with different side-effect profiles. The present study compared real-world treatment patterns with FTD/TPI and REG for mCRC in a large, representative US claims database. MATERIALS AND METHODS: Retrospective data from the US Symphony Health Solutions' Integrated Dataverse database were analyzed for adult mCRC patients receiving FTD/TPI or REG from October 2014 to July 2016...
April 21, 2018: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29783729/chlorogenic-acid-improves-the-regorafenib-effects-in-human-hepatocellular-carcinoma-cells
#10
Maria Grazia Refolo, Catia Lippolis, Nicola Carella, Aldo Cavallini, Caterina Messa, Rosalba D'Alessandro
Chlorogenic acid (CGA) is a polyphenol present in many human dietary foods. Several studies indicated a beneficial role of CGA in the prevention of cancer and an enhancement of chemotherapy when combined with CGA in the treatment of human hepatocarcinoma (HCC). Drug toxicity, resistance and subsequent disease progression represent a problem in HCC management, although treatment with the multikinase inhibitor Regorafenib improved overall survival. This study focused on the evaluation of the effects of combined treatment using both low Regorafenib concentrations and CGA as natural compound in HCC cells...
May 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783173/development-and-validation-of-an-analytical-method-for-regorafenib-and-its-metabolites-in-mouse-plasma
#11
Qiang Fu, Mingqing Chen, Shuiying Hu, Craig A McElroy, Ron H Mathijssen, Alex Sparreboom, Sharyn D Baker
An analytical method was developed for measuring the effect of OATP1B2 deficiency on plasma levels of the kinase inhibitor regorafenib and its metabolites regorafenib-N-oxide, N-desmethyl-regorafenib-N-oxide, and regorafenib-N-β-glucuronide (RG) in mice. Compounds were separated by liquid chromatography and monitored by a triple quadrupole mass spectrometer in the selected reaction monitoring mode after positive electrospray ionization. All calibration curves were linear in the selected concentration range (R2  ≥ 0...
May 5, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29783126/systemic-therapy-for-intermediate-and-advanced-hepatocellular-carcinoma-sorafenib-and-beyond
#12
REVIEW
Jean-Luc Raoul, Masatoshi Kudo, Richard S Finn, Julien Edeline, Maria Reig, Peter R Galle
The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, with sorafenib demonstrating survival benefit in the first-line setting and becoming the first systemic therapy to be approved for HCC. More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). A key recommendation in the management of patients receiving sorafenib is to promote close communication between the patient and the physician so that adverse events (AEs) are detected early and severe AEs can be prevented...
May 17, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29770170/targeted-therapy-or-immunotherapy-optimal-treatment-in-hepatocellular-carcinoma
#13
REVIEW
Merly Contratto, Jennifer Wu
Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality in the United States and the second leading cause of cancer mortality worldwide. Sorafenib is the only food and drug administration (FDA) approved as first line systemic treatment in HCC. Regorafenib and nivolumab are the only FDA approved second line treatment after progression on sorafenib. We will discuss all potential first and second line options in HCC. In addition, we also will explore sequencing treatment options in HCC, and examine biomarkers that can potentially predict benefits from treatments such as immune checkpoint inhibitor...
May 15, 2018: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29768959/challenges-of-dispensing-costly-tablets-with-short-shelf-life
#14
Mário L de Lemos, Brittney Mathers, Nadine Badry, Linda Hamata, Kelly Lo
Afatinib, trametinib and regorafenib are three costly oral oncology drugs with a short shelf-life after the original container has been opened. Their short shelf-lives are due to degradation on exposure to moisture. Therefore, manufacturers recommend them to be dispensed in the original packaging with the desiccant. However, the prescribed quantities do not always match the quantities in the original packaging, usually because of dose modifications for toxicities. This leads to potentially significant drug wastage and financial losses...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29768050/getting-up-to-date-in-the-management-of-soft-tissue-sarcoma
#15
Jean-Yves Blay
Surgery (+ radiation therapy in selected cases) is standard treatment for adult-type localized soft tissue sarcoma (STS). Accumulating randomized clinical evidence also supports adjuvant chemotherapy as a treatment option, although this remains contentious. Doxorubicin (± ifosfamide) is the standard first-line systemic treatment for advanced STS; however, newer chemotherapeutic agents may improve outcomes achieved with single-agent doxorubicin. In a Phase II study, adding olaratumab to doxorubicin markedly improved overall survival...
May 2018: Future Oncology
https://www.readbyqxmd.com/read/29764854/preclinical-antitumor-activity-of-a-novel-anti-c-kit-antibody-drug-conjugate-against-mutant-and-wild-type-c-kit-positive-solid-tumors
#16
Tinya J Abrams, Anu Connor, Christie P Fanton, Steven B Cohen, Thomas Huber, Kathy Miller, E Erica Hong, Xiaohong Niu, Janine Kline, Marjorie Ison-Dugenny, Sarah Harris, Dana B Walker, Klaus R Krauser, Francesco Galimi, Zhen Wang, Majid Ghoddusi, Keith G Mansfield, Si Tuen Lee-Hoeflich, Jocelyn Holash, Nancy Pryer, William Kluwe, Seth A Ettenberg, William R Sellers, Emma Lees, Paul Kwon, Judith A Abraham, Siew Schleyer
PURPOSE: c-KIT overexpression is well-recognized in cancers such as GIST, SCLC, melanoma, NSCLC and AML. Treatment with the small molecule inhibitors imatinib, sunitinib and regorafenib result in resistance (c-KIT mutant tumors) or limited activity (c-KIT wildtype tumors). We selected an anti-c-KIT ADC approach to evaluate the anti-cancer activity in multiple disease models. EXPERIMENTAL DESIGN: A humanized anti-c-KIT antibody LMJ729 was conjugated to the microtubule destabilizing maytansinoid, DM1, via a non-cleavable linker (SMCC)...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29749339/intestinal-perforation-after-regorafenib-usage
#17
Barış Sarıcı, Serdar Karakaş, Ufuk Uylas, Aydın Aktaş, Mustafa Dikilitaş, Cüneyt Kayaalp
No abstract text is available yet for this article.
March 2018: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
https://www.readbyqxmd.com/read/29739893/trifluridine-tipiracil-tas-102-in-refractory-metastatic-colorectal-cancer-a-multicenter-register-in-the-frame-of-the-italian-compassionate-use-program
#18
Chiara Cremolini, Daniele Rossini, Erika Martinelli, Filippo Pietrantonio, Sara Lonardi, Silvia Noventa, Emiliano Tamburini, Giovanni Luca Frassineti, Stefania Mosconi, Federico Nichetti, Sabina Murgioni, Teresa Troiani, Beatrice Borelli, Gemma Zucchelli, Alessandro Dal Maso, Vincenzo Sforza, Gianluca Masi, Carlotta Antoniotti, Maria Di Bartolomeo, Rosalba Miceli, Fortunato Ciardiello, Alfredo Falcone
BACKGROUND: TAS-102 is indicated for patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, available therapies. Given the complete inefficacy in half of patients, the lack of predictive factors, the palliative setting, and the financial and clinical toxicity, optimizing the cost-benefit ratio is crucial. The "ColonLife" nomogram allows an estimate of the 12-week life expectancy of patients with refractory mCRC. MATERIALS AND METHODS: We collected data from patients treated at eight Italian centers in the compassionate use program...
May 8, 2018: Oncologist
https://www.readbyqxmd.com/read/29732051/dual-targeting-biomimetic-delivery-for-anti-glioma-activity-via-remodeling-the-tumor-microenvironment-and-directing-macrophage-mediated-immunotherapy
#19
Pengfei Zhao, Yonghui Wang, Xuejia Kang, Aihua Wu, Weimin Yin, Yisi Tang, Jinyu Wang, Meng Zhang, Yifei Duan, Yongzhuo Huang
Tumor-associated macrophages (TAMs) are the major components in the tumor microenvironment (TME). The polarization from the protumor M2 (TAM2) to antitumor M1 (TAM1) phenotype can not only lift the immunosuppressive constraints and elicit cytotoxic T-cell immunity but also augment the chemotherapy efficacy. However, the treatment feasibility by TAM modulation in brain tumors and the mechanisms remained unknown. A dual-targeting biomimetic codelivery and treatment strategy was developed for anti-glioma activity...
March 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29723866/prognostic-factors-associated-with-postprogression-survival-in-advanced-hepatocellular-carcinoma-patients-treated-with-sorafenib-not-eligible-for-second-line-regorafenib-treatment
#20
Teiji Kuzuya, Masatoshi Ishigami, Yoji Ishizu, Takashi Honda, Kazuhiko Hayashi, Tetsuya Ishikawa, Isao Nakano, Yoshiki Hirooka, Hidemi Goto
OBJECTIVES: The aim of this study was to investigate the prognostic factors associated with postprogression survival (PPS) in advanced hepatocellular carcinoma (HCC) patients treated with sorafenib, who were not eligible for second-line treatment with regorafenib. METHODS: A total of 103 patients with radiological confirmation of progressive disease (PD) were enrolled. RESULTS: The median PPS (n = 67) was 6.1 months. Significant and independent prognostic factors at initial radiological PD associated with good PPS were an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0, the absence of macrovascular invasion (MVI), and time to progression (TTP) ≥4 months...
May 3, 2018: Oncology
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