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https://www.readbyqxmd.com/read/28818109/metastatic-colorectal-cancer-responsive-to-regorafenib-for-2-years-a-case-report
#1
Kenji Yoshino, Dai Manaka, Ryo Kudo, Shunpei Kanai, Eisei Mitsuoka, Satoshi Kanto, Shinya Hamasu, Sayuri Konishi, Ryuta Nishitai
BACKGROUND: Regorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years...
August 18, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28815316/health-related-quality-of-life-associated-with-regorafenib-treatment-in-refractory-advanced-gastric-adenocarcinoma
#2
Andrew J Martin, Emma Gibbs, Katrin Sjoquist, Nick Pavlakis, John Simes, Tim Price, Jenny Shannon, Sanjeev Gill, Vikram Jain, Geoffrey Liu, George Kannourakis, Yeul Hong Kim, Jin Won Kim, David Goldstein
BACKGROUND: The INTEGRATE phase II multinational randomized controlled trial demonstrated the activity of regorafenib on progression-free survival (PFS) in patients with refractory advanced gastric adenocarcinoma. We sought to evaluate whether these PFS gains had the potential to be offset by quality of life (QoL) impacts from treatment side effects and to thereby determine the appropriateness of continuing development to phase III. METHODS: QoL was assessed in INTEGRATE at baseline and at each 4 weeks thereafter, until discontinuation of study treatment, using the QLQ-C30, STO22, and EQ-5D questionnaires...
August 16, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28794806/recent-developments-in-the-treatment-of-metastatic-colorectal-cancer
#3
REVIEW
Jonathan M Loree, Scott Kopetz
Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28790267/-a-case-of-recurrent-colorectal-cancer-with-bilateral-ovarian-metastases-that-were-reduced-with-regorafenib-therapy
#4
Shiro Nakae, Yuya Nogi, Jun Arima, Daiki Okamoto, Naoki Urakawa, Masataka Fujikawa, Hidetoshi Gon, Atsushi Takebe, Makoto Shinzeki, Kenichi Tanaka, Hideto Senzaki
A 63-year-old woman had recurrences of metastatic rectal cancer in the lung, peritoneum, and ovary. Regorafenib was administered at 160mg/day as third-line chemotherapy. The patient developed Grade(Gr)3 hand-foot syndrome(HFS) and Gr 2 rash, but the abdominal distension and pain were relieved by the 1st course. Analgesics could be reduced and regorafenib was administrated at reduced dosage. The patient received keishi-bukuryo-gan(EK-25)and sai-rei-tou(TJ-114) for HFS. At the beginning of therapy, ovarian metastases were not reduced and showed poor contrast enhancement on CT...
July 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28790159/functional-imaging-and-circulating-biomarkers-of-response-to-regorafenib-in-treatment-refractory-metastatic-colorectal-cancer-patients-in-a-prospective-phase-ii-study
#5
Khurum Khan, Mihaela Rata, David Cunningham, Dow-Mu Koh, Nina Tunariu, Jens C Hahne, George Vlachogiannis, Somaieh Hedayat, Silvia Marchetti, Andrea Lampis, Mahnaz Darvish Damavandi, Hazel Lote, Isma Rana, Anja Williams, Suzanne A Eccles, Elisa Fontana, David Collins, Zakaria Eltahir, Sheela Rao, David Watkins, Naureen Starling, Jan Thomas, Eleftheria Kalaitzaki, Nicos Fotiadis, Ruwaida Begum, Maria Bali, Massimo Rugge, Eleanor Temple, Matteo Fassan, Ian Chau, Chiara Braconi, Nicola Valeri
OBJECTIVE: Regorafenib demonstrated efficacy in patients with metastatic colorectal cancer (mCRC). Lack of predictive biomarkers, potential toxicities and cost-effectiveness concerns highlight the unmet need for better patient selection. DESIGN: Patients with RAS mutant mCRC with biopsiable metastases were enrolled in this phase II trial. Dynamic contrast-enhanced (DCE) MRI was acquired pretreatment and at day 15 post-treatment. Median values of volume transfer constant (K(trans)), enhancing fraction (EF) and their product KEF (summarised median values of K(trans)× EF) were generated...
August 8, 2017: Gut
https://www.readbyqxmd.com/read/28781808/treatment-of-metastatic-refractory-colorectal-cancer-following-regorafenib-failure
#6
Nobumichi Takeuchi, Kumiko Koike, Sonomi Yoshida, Akiko Kudo, Nodoka Sekiguchi, Ataru Nakayama, Kouji Kubota, Takashi Rokuhara, Masayuki Kitahara
At present, there is no set strategy for the treatment of patients with colorectal cancer subsequent to the failure of standard treatment, other than the use of regorafenib (RGR) and TAS-102. The best order in which to use these drugs, and their safety and efficacy in combination with other drugs, are currently under investigation. It has been reported that RGR has a resensitizing effect on tumors that have previously failed to respond to anticancer drugs; this makes it a promising salvage therapy for colorectal cancer...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28775208/a-multikinase-and-dna-pk-inhibitor-combination-immunomodulates-melanomas-suppresses-tumor-progression-and-enhances-immunotherapies
#7
Alexander K Tsai, Asra Y Khan, Christina E Worgo, Lucy L Wang, Yuanyuan Liang, Eduardo Davila
Combination therapies have the potential to improve outcomes in melanoma patients but have not yet been clinically efficacious. Here, we used high-throughput flow cytometry-based screening to identify and characterize candidate therapies that might synergize with and augment T-cell immunotherapy efficacy. Two lead therapies, regorafenib and NU7441, were selected based on their ability to alter a variety of immunomodulatory proteins, including CD55, CD73, CD155, programmed death-ligand 1 (PD-L1), nerve growth factor receptor (NGFR), and HLA class I in a heterogeneous panel of melanomas...
August 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28768426/necrotising-fasciitis-in-a-patient-treated-with-folfiri-aflibercept-for-colorectal-cancer-a-case-report
#8
A Gonzaga-López, J Muñoz-Rodriguez, A Ruiz-Casado
Anti-angiogenics have become an important part of the treatment of several types of tumours such as ovarian, breast, lung and colorectal cancer. Necrotising fasciitis has been reported with bevacizumab but no cases have been reported with aflibercept, ramucirumab or regorafenib in patients with colorectal cancer. Necrotising fasciitis is a rare complication affecting one in 5000 bevacizumab users. We report the case of a 64-year-old man with stage IV rectosigmoid cancer under treatment with folinic acid, fluorouracil and irinotecan (FOLFIRI) and aflibercept, who developed a Fournier's gangrene...
August 3, 2017: Annals of the Royal College of Surgeons of England
https://www.readbyqxmd.com/read/28766967/regorafenib-as-treatment-for-patients-with-advanced-hepatocellular-cancer
#9
Kiruthikah Thillai, Krishnie Srikandarajah, Paul Ross
Hepatocellular carcinoma is one of the fastest growing causes of cancer-related mortality worldwide. Sorafenib was the first and only drug to improve survival for patients with advanced disease, and has been the cornerstone of treatment for nearly a decade. Regorafenib is a multikinase inhibitor that has recently been shown to significantly improve survival in patients who have progressed on first-line sorafenib. In this review, we discuss the pharmacokinetic and pharmacodynamics properties of regorafenib and its efficacy and tolerability in patients with advanced hepatocellular carcinoma...
August 2, 2017: Future Oncology
https://www.readbyqxmd.com/read/28760399/tas-102-plus-bevacizumab-for-patients-with-metastatic-colorectal-cancer-refractory-to-standard-therapies-c-task-force-an-investigator-initiated-open-label-single-arm-multicentre-phase-1-2-study
#10
Yasutoshi Kuboki, Tomohiro Nishina, Eiji Shinozaki, Kentaro Yamazaki, Kohei Shitara, Wataru Okamoto, Takeshi Kajiwara, Toshihiko Matsumoto, Takahiro Tsushima, Nobuo Mochizuki, Shogo Nomura, Toshihiko Doi, Akihiro Sato, Atsushi Ohtsu, Takayuki Yoshino
BACKGROUND: In patients with heavily treated metastatic colorectal cancer, TAS-102-a combination of trifluridine and tipiracil-has shown a significant overall survival benefit compared with placebo. In preclinical models, TAS-102 plus bevacizumab has shown enhanced activity against colorectal cancer xenografts compared with that for either drug alone. In this phase 1/2 study, we assessed the activity and safety of TAS-102 plus bevacizumab. METHODS: We did this investigator-initiated, open-label, single-arm, multicentre, phase 1/2 trial of TAS-102 plus bevacizumab in four cancer centres in Japan...
July 28, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28752706/-preparation-characterization-and-antitumor-of-cyclodextrin-inclusion-of-an-anti-cancer-drug-regorafenib
#11
Liu Kai-Hang, Sun Mengying, Tang Guping, H U Xiurong
Objective: In order to improve the drug's solubility, dissolution and bioavailability, RG-β-CD, RG-γ-CD and RG-Hp-β-CD were prepared by co-crystallization between Regorafenib (RG) and β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD) and Hydroxypropyl-β-cyclodextrin (Hp-β-CD). Methods: Three inclusion complexes were prepared by recrystallization and solvent evaporation methods and characterized by fourier transform infrared spectroscopy (FT-IR), thermal analysis (TG), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), (1)H nuclear magnetic resonance ((1)H-NMR), nuclear overhauser effect spectroscopy (NOESY)...
March 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28750235/investigation-of-the-effect-of-plasma-albumin-levels-on-regorafenib-induced-hepatotoxicity-using-a-validated-liquid-chromatography-tandem-mass-spectrometry-method
#12
Yi Yun Pang, Yeong Lan Tan, Han Kiat Ho
Regorafenib is an oral multikinase inhibitor indicated for metastatic colorectal cancer and gastrointestinal stromal tumour. Due to its extensive plasma protein binding and low calculated hepatic extraction ratio, the hepatotoxicity observed with usage of the drug may be related to its plasma exposure. To investigate the highly dynamic free:bound drug concentration for regorafenib in the plasma, a bioanalytical liquid chromatography-tandem mass spectrometric assay was developed and validated in human plasma...
July 17, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28738235/treatment-decisions-in-metastatic-colorectal-cancer-beyond-first-and-second-line-combination-therapies
#13
REVIEW
A Vogel, R D Hofheinz, S Kubicka, D Arnold
Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has reached up to 30months in recent clinical trials of first line therapies. Following disease progression after the standard in both, 1st and 2nd line, combination chemotherapy with monoclonal antibodies, many patients maintain a good performance status and a significant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important...
May 4, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28736639/promising-therapeutics-of-gastrointestinal-cancers-in-clinical-trials
#14
REVIEW
Lingling Du, Zheng Che, Andrea Wang-Gillam
Many novel therapeutics are being developed for patients with cancers along the gastrointestinal (GI) tract. These emerging agents are frequently classified by their biological targets such as tumor growth pathways, tumor metabolism, microenvironment, etc. Some agents targeting cancer growth pathways are based on existing clinically validated therapeutic targets, such as regorafenib for hepatocellular carcinoma (HCC), while other agents focus on newly identified targets, such as FGFR fusions in cholangiocarcinoma...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28733794/fatigue-associated-with-newly-approved-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-an-up-to-date-meta-analysis
#15
REVIEW
Jing Li, Jian Gu
The fatigue associated with five newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) is poorly understood. We conducted this systematic review to fully investigate the fatigue associated with these VEGFR-TKIs in cancer patients. Relevant studies of randomized controlled trials in cancer patients treated with the five VEGFR-TKIs were retrieved and a systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until March 2017...
July 21, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28721456/antiangiogenic-tyrosine-kinase-inhibitors-in-colorectal-cancer-is-there-a-path-to-making-them-more-effective
#16
REVIEW
Thomas B Karasic, Mark A Rosen, Peter J O'Dwyer
Antiangiogenic therapy has a proven survival benefit in metastatic colorectal cancer. Inhibition of the VEGF pathway using a variety of extracellular antibody approaches has clear benefit in combination with chemotherapy, while intracellular blockade using tyrosine kinase inhibitors (TKIs) such as sorafenib and regorafenib has had more limited success. Pharmacodynamic modeling using modalities such as DCE-MRI indicates potent antiangiogenic effects of these TKIs, yet numerous combination therapies, primarily with chemotherapy, have failed to demonstrate an additive benefit...
July 18, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28719584/health-policy-me-too-drugs-with-limited-benefits-the-tale-of-regorafenib-for-hcc
#17
Bishal Gyawali, Vinay Prasad
No abstract text is available yet for this article.
July 18, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28712319/primary-liver-cancer-genome-sequencing-translational-implications-and-challenges
#18
Demosthenes E Ziogas, Ioannis D Kyrochristos, Georgios K Glantzounis, Dimitrios Christodoulou, Evangelos Felekouras, Dimitrios H Roukos
The prognosis of primary liver cancer (PLC) remains poor and is explained by the slow progress in understanding the molecular pathways driving tumorigenesis, therapeutic resistance and relapse. For early PLCs, complete surgical resection is the only effective treatment, with sorafenib and, more recently, regorafenib prolonging overall survival by a few months. Areas covered: Application of next-generation sequencing (NGS), including targeted NGS (tNGS), whole-exome sequencing (WES), whole-genome sequencing (WGS) and RNA sequencing (RNAseq), on clinical samples from patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) could aid in comprehending tumorigenesis, genetic and genomic heterogeneity, as well as developing molecular classifications for specialized targeted therapy...
July 26, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28712098/precision-medicine-in-metastatic-colorectal-cancer-relevant-carcinogenic-pathways-and-targets-part-1-biologic-therapies-targeting-the-epidermal-growth-factor-receptor-and-vascular-endothelial-growth-factor
#19
REVIEW
Benjamin A Weinberg, Marion L Hartley, Mohamed E Salem
The survival of patients with metastatic colorectal cancer has improved dramatically in recent years, with overall survival exceeding 3 years in large randomized clinical trials. There are now several treatment options for patients with metastatic colorectal cancer. In addition to chemotherapy backbones utilizing fluoropyrimidine, oxaliplatin, and irinotecan combinations, biologic agents that target specific oncogenic pathways have contributed to the improved survival observed in this patient population. This class of medications includes epidermal growth factor receptor (EGFR)-targeted drugs (cetuximab and panitumumab) and vascular endothelial growth factor (VEGF)-targeted therapies (bevacizumab, ramucirumab, ziv-aflibercept, and regorafenib)...
July 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28710508/risk-of-gastrointestinal-events-with-newly-approved-after-2011-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-a-meta-analysis-of-randomized-controlled-trials
#20
REVIEW
Jing Li, Jian Gu
PURPOSE: We performed a meta-analysis to systematically review the gastrointestinal (GI) events (diarrhea, nausea, vomiting, anorexia) of five newly approved (after 2011) VEGFR-TKIs in cancer patients. METHODS: The relevant studies of the randomized controlled trials (RCTs) in cancer patients treated with cabozantinib, vandetanib, lenvatinib, regorafenib, and axitinib were retrieved and the systematic evaluation was conducted. RESULTS: Forty-one randomized controlled trials and 10,860 patients were included...
July 15, 2017: European Journal of Clinical Pharmacology
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