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https://www.readbyqxmd.com/read/28934120/angiogenesis-inhibitors-in-nsclc
#1
REVIEW
Anna Manzo, Agnese Montanino, Guido Carillio, Raffaele Costanzo, Claudia Sandomenico, Nicola Normanno, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Perrone, Gaetano Rocco, Alessandro Morabito
Angiogenesis is a complex biological process that plays a relevant role in sustaining the microenvironment, growth, and metastatic potential of several tumors, including non-small cell lung cancer (NSCLC). Bevacizumab was the first angiogenesis inhibitor approved for the treatment of patients with advanced NSCLC in combination with chemotherapy; however, it was limited to patients with non-squamous histology and first-line setting. Approval was based on the results of two phase III trials (ECOG4599 and AVAIL) that demonstrated an improvement of about two months in progression-free survival (PFS) in both trials, and in the ECOG4599 trial, an improvement in overall survival (OS) also...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28928842/significant-response-to-ramucirumab-monotherapy-in-chemotherapy-resistant-recurrent-alpha-fetoprotein-producing-gastric-cancer-a-case-report
#2
Yasuhiro Arakawa, Miho Tamura, Keisuke Aiba, Kazuhiko Morikawa, Daisuke Aizawa, Masahiro Ikegami, Masami Yuda, Katsunori Nishikawa
Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is a relatively rare type of gastric cancer characterized by a high incidence of liver and lymph node metastases, and a poor prognosis. Few advanced AFPGC cases treated successfully with conventional chemotherapy have been reported thus far. Although the development of molecular-targeted therapy has improved the prognosis of various types of cancer, there are currently no tailored therapies for AFPGC. In the present report, the case of a chemotherapy-resistant recurrent AFPGC patient who exhibited a significant response to ramucirumab monotherapy is presented...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28916371/ramucirumab-plus-docetaxel-versus-placebo-plus-docetaxel-in-patients-with-locally-advanced-or-metastatic-urothelial-carcinoma-after-platinum-based-therapy-range-a-randomised-double-blind-phase-3-trial
#3
Daniel P Petrylak, Ronald de Wit, Kim N Chi, Alexandra Drakaki, Cora N Sternberg, Hiroyuki Nishiyama, Daniel Castellano, Syed Hussain, Aude Fléchon, Aristotelis Bamias, Evan Y Yu, Michiel S van der Heijden, Nobuaki Matsubara, Boris Alekseev, Andrea Necchi, Lajos Géczi, Yen-Chuan Ou, Hasan Senol Coskun, Wen-Pin Su, Miriam Hegemann, Ivor J Percent, Jae-Lyun Lee, Marcello Tucci, Andrey Semenov, Fredrik Laestadius, Avivit Peer, Giampaolo Tortora, Sufia Safina, Xavier Garcia Del Muro, Alejo Rodriguez-Vida, Irfan Cicin, Hakan Harputluoglu, Ryan C Widau, Astra M Liepa, Richard A Walgren, Oday Hamid, Annamaria H Zimmermann, Katherine M Bell-McGuinn, Thomas Powles
BACKGROUND: Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population. METHODS: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy...
September 12, 2017: Lancet
https://www.readbyqxmd.com/read/28915702/targeted-therapies-for-gastric-cancer-failures-and-hopes-from-clinical-trials
#4
REVIEW
Maria Apicella, Simona Corso, Silvia Giordano
Gastric cancer is the third leading cause of cancer mortality worldwide. As surgery is the only curative treatment strategy and conventional chemotherapy has shown limited efficacy -with a median overall survival of 10 months- new treatments are urgently needed. Trastuzumab and Ramucirumab (targeting HER2 and VEGFR2, respectively) are the only targeted therapies approved so far. Indeed, most Phase III clinical trials evaluating molecular drugs in gastric cancer failed. This review will retrace the relevant clinical trials with molecular therapies performed in gastric cancer patients, discussing the possible reasons for their failure and indicating new perspective for a real improvement of the treatment of this disease...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913565/a-retrospective-analysis-of-ramucirumab-monotherapy-in-previously-treated-japanese-patients-with-advanced-or-metastatic-gastric-adenocarcinoma
#5
Satoshi Murahashi, Daisuke Takahari, Takeru Wakatsuki, Naoki Fukuda, Takashi Ichimura, Mariko Ogura, Masato Ozaka, Eiji Shinozaki, Izuma Nakayama, Tomohiro Matsushima, Hiroki Osumi, Keisho Chin, Kensei Yamaguchi
BACKGROUND: The REGARD trial demonstrated that ramucirumab monotherapy improved both overall survival (OS) and progression-free survival (PFS) compared with best supportive care plus placebo as second-line treatment for patients with advanced gastric cancer. However, the efficacy and safety of ramucirumab monotherapy for previously treated Japanese patients with advanced gastric cancer remains unknown. METHODS: Previously treated Japanese patients with advanced gastric cancer who received ramucirumab monotherapy between June 2015 and March 2016 at the Cancer Institute Hospital were enrolled in the study...
September 14, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28900008/targeting-cxcr4-dependent-immunosuppressive-ly6c-low-monocytes-improves-antiangiogenic-therapy-in-colorectal-cancer
#6
Keehoon Jung, Takahiro Heishi, Joao Incio, Yuhui Huang, Elizabeth Y Beech, Matthias Pinter, William W Ho, Kosuke Kawaguchi, Nuh N Rahbari, Euiheon Chung, Jun Ki Kim, Jeffrey W Clark, Christopher G Willett, Seok Hyun Yun, Andrew D Luster, Timothy P Padera, Rakesh K Jain, Dai Fukumura
Antiangiogenic therapy with antibodies against VEGF (bevacizumab) or VEGFR2 (ramucirumab) has been proven efficacious in colorectal cancer (CRC) patients. However, the improvement in overall survival is modest and only in combination with chemotherapy. Thus, there is an urgent need to identify potential underlying mechanisms of resistance specific to antiangiogenic therapy and develop strategies to overcome them. Here we found that anti-VEGFR2 therapy up-regulates both C-X-C chemokine ligand 12 (CXCL12) and C-X-C chemokine receptor 4 (CXCR4) in orthotopic murine CRC models, including SL4 and CT26...
September 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28893090/an-in-depth-review-of-chemical-angiogenesis-inhibitors-for-treating-hepatocellular-carcinoma
#7
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
https://www.readbyqxmd.com/read/28888797/will-molecular-target-agents-enable-the-multidisciplinary-treatment-in-stage-iv-gastric-cancer
#8
REVIEW
Kozo Kataoka, Angélique Deleersnijder, Florian Lordick
A detailed molecular characterization of gastric cancer has been revealed by global initiatives and a number of new molecular agents are under investigation. Currently only trastuzumab, a monoclonal antibody for human epidermal growth factor receptor 2 (HER2), is clinically used for HER2 positive advanced gastric cancer patients and ramucirumab, a monoclonal antibody directed against the extracellular ligand-binding domain of vascular endothelial growth factor receptor (VEGFR)2, can be used in second line. However, despite the progress in gastric cancer treatment, the prognosis of stage IV gastric cancer patients remains dismal...
August 30, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28881856/strategies-targeting-angiogenesis-in-advanced-non-small-cell-lung-cancer
#9
REVIEW
Jun Wang, Jianpeng Chen, Yan Guo, Baocheng Wang, Huili Chu
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28833321/population-pharmacokinetic-meta-analysis-of-ramucirumab-in-cancer-patients
#10
Lisa O'Brien, Paul Westwood, Ling Gao, Michael Heathman
AIM: Ramucirumab is a human IgG1 monoclonal antibody that specifically binds vascular endothelial growth factor receptor-2 (VEGFR-2) and blocks binding of VEGF-A, VEGF-C, and VEGF-D. The objective of the analysis was to characterize the clinical pharmacology profile of ramucirumab using a population pharmacokinetic approach. METHODS: A total of 1639 patients with 6427 serum concentrations from 11 Phase 1b, 2, and 3 clinical trials in patients with various cancer indications were included in the analysis...
August 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28818671/incidence-and-risk-of-cardiotoxicity-in-cancer-patients-treated-with-targeted-therapies
#11
REVIEW
Matteo Santoni, Federico Guerra, Alessandro Conti, Alessandra Lucarelli, Silvia Rinaldi, Laura Belvederesi, Alessandro Capucci, Rossana Berardi
BACKGROUND: Cardiotoxicityis a serious side effect of molecularly targeted agents. The purpose of this study was to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade cardiotoxicity in patients with solid tumors receiving targeted agents through a revised meta-analysis of available clinical trials. METHODS: The scientific literature regarding cardiotoxicity was extensively analyzed using MEDLINE, PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL)...
September 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28794648/cost-analysis-of-adverse-events-associated-with-non-small-cell-lung-cancer-management-in-france
#12
Christos Chouaid, Delphine Loirat, Emilie Clay, Aurélie Millier, Chloé Godard, Amira Fannan, Laurie Lévy-Bachelot, Eric Angevin
BACKGROUND: Adverse events (AEs) related to medical treatments in non-small cell lung cancer (NSCLC) are frequent and need an appropriate costing in health economic models. Nevertheless, data on costs associated with AEs in NSCLC are scarce, particularly since the development of immunotherapy with specific immune-related AEs. OBJECTIVE: To estimate the costs of grades 3 and 4 AEs related to NSCLC treatments including immunotherapy in France. METHODS: Grades 3 and 4 AEs related to treatment and reported in at least 1% of patients in Phase III clinical trials for erlotinib, ramucirumab plus docetaxel, docetaxel, pemetrexed plus carboplatin plus bevacizumab, platinum-based chemotherapies, nivolumab and pembrolizumab were identified...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28770623/angiogenesis-inhibitors-in-early-development-for-gastric-cancer
#13
REVIEW
Mauricio P Pinto, Gareth I Owen, Ignacio Retamal, Marcelo Garrido
Angiogenesis, or the generation of new blood vessels from pre-existent ones is a critical process for tumor growth and progression. Hence, the development of angiogenesis inhibitors with therapeutic potential has been a central focus for researchers. Most angiogenesis inhibitors target the Vascular Endothelial Growth Factor (VEGF) pathway, however a number of tyrosine kinase inhibitors (TKIs), immunomodulatory drugs (IMiDs) and inhibitors of the mammalian Target-Of-Rapamycin (mTOR) pathway also display antiangiogenic activity...
September 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28768426/necrotising-fasciitis-in-a-patient-treated-with-folfiri-aflibercept-for-colorectal-cancer-a-case-report
#14
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/28767454/acneiform-rash-with-ramucirumab-and-paclitaxel-in-a-patient-with-recurrent-esophageal-cancer
#15
Donald C Moore
No abstract text is available yet for this article.
July 17, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28744667/exposure-response-relationship-of-ramucirumab-in-patients-with-advanced-second-line-colorectal-cancer-exploratory-analysis-of-the-raise-trial
#16
Allen Lee Cohn, Takayuki Yoshino, Volker Heinemann, Radka Obermannova, György Bodoky, Jana Prausová, Rocio Garcia-Carbonero, Tudor Ciuleanu, Pilar Garcia-Alfonso, David C Portnoy, Eric Van Cutsem, Kentaro Yamazaki, Philip R Clingan, Jonathon Polikoff, Sara Lonardi, Lisa M O'Brien, Ling Gao, Ling Yang, David Ferry, Federico Nasroulah, Josep Tabernero
PURPOSE: To characterize ramucirumab exposure-response relationships for efficacy and safety in patients with metastatic colorectal cancer (mCRC) using data from the RAISE study. METHODS: Sparse pharmacokinetic samples were collected; a population pharmacokinetic analysis was conducted. Univariate and multivariate Cox proportional hazards models analyzed the relationship between predicted ramucirumab minimum trough concentration at steady state (C min,ss) and survival...
July 25, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28744168/spotlight-on-ramucirumab-in-the-treatment-of-nonsmall-cell-lung-cancer-design-development-and-clinical-activity
#17
REVIEW
Manuel Cobo, Vanesa Gutiérrez, Rosa Villatoro, Jose Manuel Trigo, Inmaculada Ramos, Omar López, María Ruiz, Ana Godoy, Irene López, Macarena Arroyo
The vascular endothelial growth factor (VEGF) and receptor is a therapeutic target because of the importance of this pathway in carcinogenesis. This pathway regulates and promotes angiogenesis as well as increases endothelial cell proliferation, permeability, and cancer survival. Ramucirumab is a new fully human monoclonal antibody that targets the VEGF receptor-2, an important key receptor implicated in angiogenesis. Ramucirumab has been approved for the treatment of second-line advanced or metastatic non-small cell lung cancer (NSCLC) in combination with the chemotherapy agent docetaxel...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28736637/primary-and-acquired-resistance-to-biologic-therapies-in-gastrointestinal-cancers
#18
REVIEW
Sam J Lubner, Nataliya V Uboha, Dustin A Deming
Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736636/biological-agents-in-gastrointestinal-cancers-adverse-effects-and-their-management
#19
REVIEW
Nivedita Arora, Arjun Gupta, Preet Paul Singh
Biological therapy comprises agents that by virtue of their unique mechanisms of action, are able to specifically incite a response against or target malignant cells. They differ from conventional chemotherapy with regard to mechanisms of action, indications and side effect profile. Biologic agents have revolutionized therapy for a number of malignancies. In the setting of gastrointestinal (GI) malignancies, agents targeting vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (Her2/Neu) and epidermal growth factor receptor (EGFR) have proven to be invaluable additions to chemotherapy...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736629/biologic-therapy-in-esophageal-and-gastric-malignancies-current-therapies-and-future-directions
#20
REVIEW
Pamela Samson, A Craig Lockhart
Biologic agents, including targeted antibodies as well as immunomodulators, are demonstrating unparalleled development and study across the entire spectrum of human malignancy. This review summarizes the current state of biologic therapies for esophageal, esophagogastric, and gastric malignancies, including those that target human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), c-Met, mechanistic target of rapamycin (mTOR) and immunomodulators...
June 2017: Journal of Gastrointestinal Oncology
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