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https://www.readbyqxmd.com/read/29049226/regorafenib-induced-retinal-and-gastrointestinal-hemorrhage-in-a-metastatic-colorectal-cancer-patient-with-liver-dysfunction-a-case-report
#1
Kenji Tsuchihashi, Hozumi Shimokawa, Kotoe Takayoshi, Kenta Nio, Tomomi Aikawa, Yuzo Matsushita, Iori Wada, Shuji Arita, Hiroshi Ariyama, Hitoshi Kusaba, Koh-Hei Sonoda, Koichi Akashi, Eishi Baba
RATIONALE: Regorafenib is effective for metastatic colorectal cancer but its toxicity such as hemorrhage should be considered. The safety of regorafenib for the patient with the liver disease is not known. PATIENT CONCERNS: Seventy-one-year old man of colon cancer had myodesopsia and blood stool after 14 days from the initiation of regorafenib administration with 50% dose reduction due to liver dysfunction. DIAGNOSES: Fundus examination revealed hemorrhage of the retinal vein...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29040994/sorafenib-regorafenib-sequential-therapy-in-advanced-hepatocellular-carcinoma-a-single-institute-experience
#2
Kazuomi Ueshima, Naoshi Nishida, Masatoshi Kudo
OBJECTIVES: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29036035/the-treatment-path-in-hepatocellular-carcinoma
#3
Hashem B El-Serag, Andrew X Zhu, Matthew S Johnson
The treatment approach for hepatocellular carcinoma (HCC) depends on the stage and extent of disease, the severity of the underlying liver disease, and the overall performance status of the patient. Treatment consists of 4 main strategies: surgery (eg, resection and liver transplant), locoregional procedures (eg, ablation and transarterial embolization), systemic therapies, and best supportive care. For patients with early-stage tumors, surgical treatment or ablation can be curative. Patients with intermediate-stage disease can be candidates for embolization, administered as either transarterial chemoembolization (TACE) or transarterial radioembolization (TARE)...
August 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29034773/substrate-dependent-effects-of-molecular-targeted-anticancer-agents-on-activity-of-organic-anion-transporting-polypeptide-1b1
#4
Hiroyoshi Koide, Masayuki Tsujimoto, Ai Takeuchi, Miyu Tanaka, Yoko Ikegami, Mayu Tagami, Syoko Abe, Miki Hashimoto, Tetsuya Minegaki, Kohshi Nishiguchi
1. Organic anion-transporting polypeptide 1B1 (OATP1B1) plays an important role in the hepatic uptake of a broad range of substrate drugs. In vitro experiments show that molecular-targeted agents do not always have similar effects on OATP1B1 activity. 2. The purpose of this study was to clarify whether the effects of molecular-targeted agents on OATP1B1 are substrate-dependent. We used OATP1B1-transfected cells to compare the effects of molecular-targeted agents on OATP1B1-mediated uptake of fluorescein (FL), 2',7'-dichlorofluorescein (DCF), atorvastatin, SN-38, and valsartan...
October 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29022151/comparative-safety-of-targeted-therapies-for-metastatic-colorectal-cancer-between-elderly-and-younger-patients-a-study-using-the-international-pharmacovigilance-database
#5
Amandine Gouverneur, Pauline Claraz, Marine Rousset, Mickaël Arnaud, Annie Fourrier-Réglat, Antoine Pariente, Thomas Aparicio, Ghada Miremont-Salamé, Pernelle Noize
BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly. OBJECTIVE: This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life. PATIENTS AND METHODS: An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed...
October 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29021377/a-comprehensive-review-of-sequencing-and-combination-strategies-of-targeted-agents-in-metastatic-colorectal-cancer
#6
REVIEW
Kristen K Ciombor, Tanios Bekaii-Saab
The emergence of targeted therapies for the treatment of metastatic colorectal cancer (mCRC) has considerably improved survival, but has resulted in a dilemma of identifying the optimal sequence and combination of various agents in the mCRC treatment landscape. A number of cytotoxic agents, including irinotecan, oxaliplatin, 5-fluorouracil, capecitabine, and TAS-102, are available for treatment of mCRC. Additionally, whereas patients harboring rat sarcoma viral oncogene homolog (RAS)-wild type mCRC can be treated with the anti-epidermal growth factor receptor antibodies cetuximab and panitumumab or antiangiogenic agents (bevacizumab, ziv-aflibercept, and ramucirumab), patients with RAS-mutant mCRC are limited to antiangiogenic agents as biologic options...
October 11, 2017: Oncologist
https://www.readbyqxmd.com/read/29018575/clinical-outcome-of-patients-with-chemorefractory-metastatic-colorectal-cancer-treated-with-trifluridine-tipiracil-tas-102-a-single-italian-institution-compassionate-use-programme
#7
Vincenzo Sforza, Erika Martinelli, Claudia Cardone, Giulia Martini, Stefania Napolitano, Pietro Paolo Vitiello, Pasquale Vitale, Nicoletta Zanaletti, Alfonso Reginelli, Maurizio Di Bisceglie, Tiziana Pia Latiano, Anna Maria Bochicchio, Fabiana Cecere, Francesco Selvaggi, Fortunato Ciardiello, Teresa Troiani
BACKGROUND: TAS-102 improves overall survival (OS) in patients with metastatic colorectal cancer (mCRC) refractory to standard treatments. However, predictive biomarkers of efficacy are currently lacking. PATIENTS AND METHODS: We treated a cohort of 43 chemorefractory mCRC patients treated with TAS-102, in a single institution expanded access, compassionate use programme. We stratified patients in two groups according to number of cycles received (<6 cycles and ≥6 cycles)...
2017: ESMO Open
https://www.readbyqxmd.com/read/28992563/potential-role-of-polymorphisms-in-the-transporter-genes-ent1-and-mate1-oct2-in-predicting-tas-102-efficacy-and-toxicity-in-patients-with-refractory-metastatic-colorectal-cancer
#8
Mitsukuni Suenaga, Marta Schirripa, Shu Cao, Wu Zhang, Dongyun Yang, Vincenzo Dadduzio, Lisa Salvatore, Beatrice Borelli, Filippo Pietrantonio, Yan Ning, Satoshi Okazaki, Martin D Berger, Yuji Miyamoto, Roel Gopez, Afsaneh Barzi, Toshiharu Yamaguchi, Fotios Loupakis, Heinz-Josef Lenz
BACKGROUND: Trifluridine (FTD) is an active cytotoxic component of the metastatic colorectal cancer (mCRC) drug TAS-102, and thymidine phosphorylase inhibitor (TPI) inhibits the rapid degradation of FTD. We tested whether single nucleotide polymorphisms (SNPs) in genes involved in FTD metabolism and TPI excretion could predict outcome in patients with mCRC treated with TAS-102. PATIENTS AND METHODS: We investigated three different cohorts: a training cohort (n = 52) and a testing cohort (n = 129) both receiving TAS-102 and a control cohort (n = 52) receiving regorafenib...
October 6, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28985760/an-improved-pre-clinical-patient-derived-liquid-xenograft-mouse-model-for-acute-myeloid-leukemia
#9
Zhisheng Her, Kylie Su Mei Yong, Kathirvel Paramasivam, Wilson Wei Sheng Tan, Xue Ying Chan, Sue Yee Tan, Min Liu, Yong Fan, Yeh Ching Linn, Kam Man Hui, Uttam Surana, Qingfeng Chen
BACKGROUND: Xenotransplantation of patient-derived AML (acute myeloid leukemia) cells in NOD-scid Il2rγ (null) (NSG) mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. METHODS: Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically...
October 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28978118/regorafenib-in-combination-with-silybin-as-a-novel-potential-strategy-for-the-treatment-of-metastatic-colorectal-cancer
#10
Valentina Belli, Vincenzo Sforza, Claudia Cardone, Erika Martinelli, Giusi Barra, Nunzia Matrone, Stefania Napolitano, Floriana Morgillo, Concetta Tuccillo, Alessandro Federico, Marcello Dallio, Carmelina Loguercio, Antonietta Gerarda Gravina, Raffaele De Palma, Fortunato Ciardiello, Teresa Troiani
PURPOSE: Regorafenib, an oral multikinase inhibitor, has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients that have progressed after all standard therapies. However, novel strategies to improve tolerability and enhance anti-cancer efficacy are needed. EXPERIMENTAL DESIGN: We have evaluated in vitro the effects of regorafenib in combination with silybin, a biologically active component extracted from the seeds of Silybum marianum, in a panel of human colon cancer cells...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966584/fatal-acute-liver-failure-as-a-consequence-of-regorafenib-treatment-in-a-metastatic-colon-cancer
#11
Dominique Béchade, Marie Desjardin, Claire Castain, Pierre-Henri Bernard, Marianne Fonck
Regorafenib is a multikinase inhibitor which showed benefits in pretreated metastatic colorectal cancer patients. Hepatotoxicity has been described as a frequent side effect. We report the case of a 65-year-old patient presenting with jaundice, fever, and hepatocellular insufficiency which led to death of the patient. She had previously been treated with several lines of chemotherapy for sub- and diaphragmatic ganglionic metastases of a colon adenocarcinoma. There were no liver metastases. The fatal liver failure occurred at the beginning of treatment with regorafenib at a dosage of 3 tablets per day...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28954993/regorafenib-induces-adaptive-resistance-of-colorectal-cancer-cells-via-inhibition-of-vascular-endothelial-growth-factor-receptor
#12
Chisato Tomida, Hikaru Nagano, Naoko Yamagishi, Takayuki Uchida, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa, Shigetada Teshima-Kondo
Recently, inhibition of tumor angiogenesis has become an important anti-cancer therapy. Tumor angiogenesis is regulated by multiple signaling pathways, including VEGF and VEGF receptor (VEGF-R), FGF and FGF receptor (FGF-R), and PDGF and PDGF receptor (PDGF-R) pathways. Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28938279/regorafenib-treatment-for-management-of-colorectal-cancer-a-systematic-review-and-meta-analysis-of-6-randomized-controlled-trials
#13
Yang Wang, ShengZhuo Liu, Shan Liu, Xia Li, QiuYan Liu, XiaoLan Zou, Min Zhu, YongXin Jiang
No abstract text is available yet for this article.
September 21, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28936569/treatment-related-serious-adverse-events-and-fatal-adverse-events-with-regorafenib-in-cancer-patients-a-meta-analysis-of-phase-3-randomized-controlled-trials
#14
REVIEW
Meihui Cao, Feifei Li, Yue Wang, Jingdong Zhang
Regorafenib (Stivarga) is an oral small-molecule multikinase inhibitor commonly used against a variety of cancers. We performed a meta-analysis of all phase 3 randomized controlled trials (RCTs) of regorafenib to quantify the increased risk of SAEs and FAEs. We carried out a systematic search of electronic databases for studies published from inception to February 2017 without any restrictions. Eligibility criteria included phase 3 RCTs of tumors comparing regorafenib, alone or in combination with non-targeted chemotherapy (regorafenib arm) versus placebo or non-targeted chemotherapy (control arm)...
September 22, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28936405/chemotherapy-for-hepatocellular-carcinoma-current-evidence-and-future-perspectives
#15
REVIEW
Emanuele Rinninella, Lucia Cerrito, Irene Spinelli, Marco Cintoni, Maria Cristina Mele, Maurizio Pompili, Antonio Gasbarrini
Hepatocarcinogenesis is a multistep process, heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant neoangiogenesis. Understanding the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these pathways. As hepatocellular carcinoma has higher arterial vascularization than normal liver, this could be a good target for novel molecular therapies. Introduction of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this tumor...
September 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28932966/regorafenib-in-advanced-hepatocellular-carcinoma-hcc-considerations-for-treatment
#16
Kyung Kim, Reena Jha, Petra A Prins, Hongkun Wang, Monica Chacha, Marion L Hartley, Aiwu Ruth He
PURPOSE: We report our institutional observations of ten patients with advanced hepatocellular carcinoma (HCC) (seven and three were Child-Pugh class A and B, respectively) who received compassionate regorafenib therapy between June 2016 and January 2017. These patients did not fit the rigid criteria of a clinical trial and represented the use of regorafenib in an everyday clinic situation. METHODS: Regorafenib (160 mg P.O. daily) was administered to patients on a 4-week cycle (3 weeks on, 1 week off) until disease progression (assessed using mRECIST criteria) or discontinuation secondary to toxicity (assessed using CTCAE criteria)...
September 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28915719/genomic-analysis-of-exceptional-responder-to-regorafenib-in-treatment-refractory-metastatic-rectal-cancer-a-case-report-and-review-of-the-literature
#17
Krittiya Korphaisarn, Jonathan M Loree, Van Nguyen, Ryanne Coulson, Vijaykumar Holla, Beate C Litzenburger, Ken Chen, Gordon B Mills, Dipen M Maru, Funda Meric-Bernstan, Kenna R Mills Shaw, Scott Kopetz
We present the case of a 53-year-old male with metastatic rectal cancer who was treatment resistant to FOLFOX and FOLFOXIRI. Due to a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, regorafenib was given in the third line setting. Surprisingly, the patient had a prolonged partial response that lasted 27 months. Mutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for this unusual event. A poorly characterized but nontransforming mutation in Fms-like tyrosine kinase 4 (FLT4) was present in the tumor...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900283/a-multiplex-preclinical-model-for-adenoid-cystic-carcinoma-of-the-salivary-gland-identifies-regorafenib-as-a-potential-therapeutic-drug
#18
Chen Chen, Sujata Choudhury, Darawalee Wangsa, Chamille J Lescott, Devan J Wilkins, Praathibha Sripadhan, Xuefeng Liu, Danny Wangsa, Thomas Ried, Christopher Moskaluk, Michael J Wick, Eric Glasgow, Richard Schlegel, Seema Agarwal
Adenoid cystic carcinomas (ACC) are rare salivary gland cancers with a high incidence of metastases. In order to study this tumor type, a reliable model system exhibiting the molecular features of this tumor is critical, but none exists, thereby inhibiting in-vitro studies and the analysis of metastatic behavior. To address this deficiency, we have coupled an efficient method to establish tumor cell cultures, conditional reprogramming (CR), with a rapid, reproducible and robust in-vivo zebrafish model. We have established cell cultures from two individual ACC PDX tumors that maintain the characteristic MYB translocation...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894015/propensity-score-analysis-of-regorafenib-versus-trifluridine-tipiracil-in-patients-with-metastatic-colorectal-cancer-refractory-to-standard-chemotherapy-regotas-a-japanese-society-for-cancer-of-the-colon-and-rectum-multicenter-observational-study
#19
Toshikazu Moriwaki, Shota Fukuoka, Hiroya Taniguchi, Atsuo Takashima, Yusuke Kumekawa, Takeshi Kajiwara, Kentaro Yamazaki, Taito Esaki, Chinatsu Makiyama, Tadamichi Denda, Hironaga Satake, Takeshi Suto, Naotoshi Sugimoto, Masanobu Enomoto, Toshiaki Ishikawa, Tomomi Kashiwada, Masahiko Sugiyama, Yoshito Komatsu, Hiroyuki Okuyama, Eishi Baba, Daisuke Sakai, Tomoki Watanabe, Takao Tamura, Kimihiro Yamashita, Masahiko Gosho, Yasuhiro Shimada
BACKGROUND: This study compared the efficacy of regorafenib and trifluridine/tipiracil (TFTD) in patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy, because despite their clinical approval, it still remains unclear which of these two drugs should be used as initial treatment. MATERIALS AND METHODS: The clinical data of patients with mCRC who were treated with regorafenib or TFTD and those of drug-naive patients, between June 2014 and September 2015, were retrospectively collected from 24 institutions in Japan...
September 11, 2017: Oncologist
https://www.readbyqxmd.com/read/28893090/an-in-depth-review-of-chemical-angiogenesis-inhibitors-for-treating-hepatocellular-carcinoma
#20
Jean-Luc Raoul, Marine Gilabert, Xavier Adhoute, Julien Edeline
Hepatocellular carcinoma (HCC) is a frequent and severe complication of cirrhosis. Most HCC patients initially present with or progress to advanced stage disease and require systemic treatment. As hypervascularization is a major characteristic of HCC, antiangiogenic drugs have been tested. Areas covered: In this review, we summarize data on the use of drugs targeting the angiogenesis. Despite many trials, in 2017 only 3 drugs, all antiangiogenic, have demonstrated efficacy in first (sorafenib, lenvatinib) or second line (regorafenib) treatment of advanced HCC...
October 2017: Expert Opinion on Pharmacotherapy
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