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Catalina Mosquera, Dino Maglic, Emmanuel E Zervos
Molecular targeted therapy is widely utilized and effective in a number of solid tumors. In pancreatic adenocarcinoma, targeted therapy has been extensively evaluated; however, survival improvement of this aggressive disease using a targeted strategy has been minimal. The purpose of this study is to review therapeutic molecular targets in completed and ongoing later phase (II and III) clinical trials to have a better understanding of the rationale and progress towards targeted molecular therapies for pancreatic cancer...
August 2, 2016: Cancer Genetics
G Aichinger, G Pahlke, L J Nagel, W Berger, D Marko
Erlotinib (Tarceva®) is a chemotherapeutic drug approved for the treatment of pancreatic cancer and non-small cell lung cancer. Its primary mode of action is the inhibition of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK). Recently, RTK-inhibiting polyphenols have been reported to interact synergistically with erlotinib. Furthermore some anthocyanidins and anthocyanin-rich berry extracts have been reported to inhibit tyrosine kinases, including the EGFR, which raises the question of potential interactions with erlotinib...
August 10, 2016: Food & Function
Peter H Ahn, Mitchell Machtay, Pramila R Anne, David Cognetti, William M Keane, Evan Wuthrick, Adam P Dicker, Rita S Axelrod
OBJECTIVES: Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. METHODS: Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve...
July 7, 2016: American Journal of Clinical Oncology
Yordan Benhamou, Vincent Picco, Hélène Raybaud, Anne Sudaka, Emmanuel Chamorey, Sanja Brolih, Martino Monteverde, Marco Merlano, Cristiana Lo Nigro, Damien Ambrosetti, Gilles Pagès
Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer worldwide. Treatments including surgery, radio- and chemo-therapies mostly result in debilitating side effects. Thus, a more accurate evaluation of patients at risk of recurrence after radio/chemo treatment is important for preserving their quality of life. We assessed whether the Telomeric Repeat-binding Factor 2 (TERF2) influences tumor aggressiveness and treatment response. TERF2 is over-expressed in many cancers but its correlation to patient outcome remains controversial in OSCC...
June 14, 2016: Oncotarget
Shiran Shapira, Shlomo Pleban, Diana Kazanov, Peter Tirosh, Nadir Arber
BACKGROUND: Terpinen-4-ol, a naturally occurring monoterpene is the main bioactive component of tea-tree oil and has been shown to have many biological activities. AIM: To study the antitumor effects of terpinen-4-ol and its mechanism of action in prostate and GI malignancies, alone and in combination with chemotherapeutic and biological agents. METHODS: Terpinen-4-ol was administrated alone or combined with standard chemotherapy (Oxaliplatin, Fluorouracil, Gemcitabine, Tarceva) and biological agent (Cetuximab)...
2016: PloS One
Jiezhong Chen, Kristin Kaley, Marie Carmel Garcon, Teresa Rodriguez, Muhammad Wasif Saif
BACKGROUND: The objective of this study was to report a case series on the efficacy and safety of capecitabine 7/7 schedule combined with erlotinib (CAP-ERL) in patients with advanced pancreatic cancer (APC) who have failed prior therapies. METHODS: We retrospectively evaluated 13 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine or oxaliplatin-irinotecan-based first-line regimens. Treatment consisted of capecitabine (Xeloda) at a flat dose of 1000 mg orally twice daily on days 1-7 out of 14 days (7/7 schedule) and erlotinib (Tarceva) 100 mg orally once daily until unacceptable toxicity or disease progression...
March 2016: Therapeutic Advances in Gastroenterology
Keunchil Park, Chong-Jen Yu, Sang-We Kim, Meng-Chih Lin, Virote Sriuranpong, Chun-Ming Tsai, Jong-Seok Lee, Jin-Hyoung Kang, K C Allen Chan, Pablo Perez-Moreno, Peter Button, Myung-Ju Ahn, Tony Mok
IMPORTANCE: Continuing molecularly targeted treatment beyond disease progression in non-small-cell lung cancer (NSCLC) has appeared promising in retrospective analyses, highlighting the challenge to identify whether progression is the optimal time to switch treatment. OBJECTIVE: To study the efficacy of first-line erlotinib therapy in patients with NSCLC with activating EGFR mutations and postprogression erlotinib therapy. DESIGN, SETTING, AND PARTICIPANTS: ASPIRATION (Asian Pacific trial of Tarceva as first-line in EGFR mutation) was a phase 2, open-label, single-arm study conducted from 2011 to 2012 in 23 centers in Hong Kong, Korea, Taiwan, and Thailand of adults with stage IV, EGFR mutation-positive NSCLC, with ECOG performance status 0 to 2...
March 2016: JAMA Oncology
Naoya Yamazaki, Yoshio Kiyohara, Shoji Kudoh, Akihiro Seki, Masahiro Fukuoka
BACKGROUND: Skin toxicities, such as rash, are the most common adverse reactions associated with erlotinib. Steroids are a key treatment option for rash management; however, optimal timing of administration and selection of steroid strength have not been fully established. In this surveillance study of Japanese non-small-cell lung cancer (NSCLC) patients treated with erlotinib, rash management using topical steroids was analyzed in routine clinical practice. METHODS: From December 2007 to October 2009, all recurrent/advanced NSCLC patients in Japan treated with erlotinib were enrolled into this study (POst-Launch All-patient Registration Surveillance in TARceva)...
April 2016: International Journal of Clinical Oncology
Raymond U Osarogiagbon, Federico Cappuzzo, Tudor Ciuleanu, Larry Leon, Barbara Klughammer
BACKGROUND: The clinical benefit of erlotinib in treating epidermal growth factor receptor (EGFR) wildtype non-small cell lung cancer (NSCLC) has been questioned. We examined the impact of erlotinib in confirmed EGFR wildtype patients in two placebo-controlled phase III trials: the National Cancer Institute of Canada Clinical Trials Group BR.21 (BR.21) and Sequential Tarceva in Unresectable Non-Small Cell Lung Cancer (SATURN) trials. METHODS: Combined re-analysis of progression-free survival (PFS) and overall survival (OS) in patients with known wildtype EGFR, estimated by Kaplan-Meier curves and compared by two-sided log-rank test...
August 2015: Translational Lung Cancer Research
Yan Cui, Jie Xu, Liang Xin, Ye Tian, Zhongli Zhan, Daliang Qi
OBJECTIVE: To explore characteristic gene mutations in nonsmall-cell lung carcinoma (NSCLC) patients with wild-type epidermal growth factor receptor (EGFR) and sensitivity to Tarceva therapy; to observe the efficacy and safety of Tarceva therapy for NSCLC patients with wild-type EGFR. MATERIALS AND METHODS: NSCLC patients with wild-type EGFR and KRAS were selected. Their tumor specimens were assessed for mutations in seven key genes in pathways downstream of EGFR, including HRAS, NRAS, BRAF, PIK3CA, AKT1, MEK1, and PTEN...
August 2015: Journal of Cancer Research and Therapeutics
Denis Soulières, Fred R Hirsch, Frances A Shepherd, Walter Bordogna, Paul Delmar, David S Shames, Barbara Klughammer
INTRODUCTION: EGFR mutations and anaplastic lymphoma kinase rearrangements are, to date, the only approved biomarkers to select treatment for non-small-cell lung cancer (NSCLC). However, there is considerable interest in identifying other predictive markers. The PTPRF gene has been suggested as a marker of interest in NSCLC and other tumor types. METHODS: This hypothesis-generating retrospective analysis examined data from two studies of erlotinib in NSCLC, Marker Identification Trial (MERIT; n = 102) and Sequential Tarceva in Unresectable NSCLC (SATURN; n = 262), to determine whether PTPRF expression was prognostic and/or predictive of patient outcomes...
September 2015: Journal of Thoracic Oncology
Soudabeh Sabetian, Mohd Shahir Shamsir
BACKGROUND: Sperm-egg interaction defect is a significant cause of in-vitro fertilization failure for infertile cases. Numerous molecular interactions in the form of protein-protein interactions mediate the sperm-egg membrane interaction process. Recent studies have demonstrated that in addition to experimental techniques, computational methods, namely protein interaction network approach, can address protein-protein interactions between human sperm and egg. Up to now, no drugs have been detected to treat sperm-egg interaction disorder, and the initial step in drug discovery research is finding out essential proteins or drug targets for a biological process...
2015: BMC Systems Biology
Janette Greenhalgh, Adrian Bagust, Angela Boland, Kerry Dwan, Sophie Beale, Juliet Hockenhull, Christine Proudlove, Yenal Dundar, Marty Richardson, Rumona Dickson, Anna Mullard, Ernie Marshall
BACKGROUND: Lung cancer is the second most diagnosed cancer in the UK. Over 70% of lung cancers are non-small cell lung cancers (NSCLCs). Patients with stage III or IV NSCLC may be offered treatment to improve survival, disease control and quality of life. One-third of these patients receive further treatment following disease progression; these treatments are the focus of this systematic review. OBJECTIVES: To appraise the clinical effectiveness and cost-effectiveness of erlotinib [Tarceva(®), Roche (UK) Ltd] and gefitinib (IRESSA(®), AstraZeneca) compared with each other, docetaxel or best supportive care (BSC) for the treatment of NSCLC after disease progression following prior chemotherapy...
June 2015: Health Technology Assessment: HTA
Katharina Schremser, Wolf H Rogowski, Sigrid Adler-Reichel, Amanda L H Tufman, Rudolf M Huber, Björn Stollenwerk
BACKGROUND: Lung cancer is among the top causes of cancer-related deaths. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors can increase progression-free survival compared with standard chemotherapy in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). OBJECTIVE: The aim of the study was to evaluate the cost-effectiveness of EGFR mutation analysis and first-line therapy with erlotinib for mutation-positive patients compared with non-individualized standard chemotherapy from the perspective of German statutory health insurance...
November 2015: PharmacoEconomics
Yisheng Huang, Li Zhang, Yuankai Shi, Shenglin Ma, Meilin Liao, Chunxue Bai, Qingyuan Zhang, Changli Wang, Feng Luo, Shiying Yu, Shukui Qin, Xiuyi Zhi, Caicun Zhou
OBJECTIVE: This study is to analyze the data of Chinese subpopulation in the Tarceva Lung Cancer Survival Treatment Study (TRUST-China) which was a global Phase IV study designed to provide erlotinib to previously treated patients with Stage IIIB/IV non-small cell lung cancer. METHODS: Patients with pathologically confirmed, unresectable Stage IIIB/IV non-small cell lung cancer who were previously failed on or unsuitable for chemotherapy or radiotherapy were given erlotinib (150 mg/day, oral) until disease progression, intolerable toxicity or death...
June 2015: Japanese Journal of Clinical Oncology
Pingping Lin, Fengmei An, Xia Xu, Liyan Zhao, Liang Liu, Ning Liu, Peipei Wang, Jiao Liu, Le Wang, Mingchun Li
Receptor tyrosine kinases, mediators of a variety of critical cellular functions, contribute to tumor progression and metastasis. The epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase family, is ubiquitously expressed on the surface of mammalian cells. Erlotinib hydrochloride (Tarceva) can inhibit the intracellular phosphorylation of tyrosine kinases. To investigate the influence of dosing time on the ability of erlotinib to inhibit tumor growth and the underlying molecular mechanisms via the PI3K/AKT and ERK/MAPK pathway, we established nude mice HCC827 tumor xenografts models...
May 1, 2015: Biochemical and Biophysical Research Communications
Imoh S Okon, Kathleen A Coughlan, Miao Zhang, Qiongxin Wang, Ming-Hui Zou
Therapeutic benefits offered by tyrosine kinase inhibitors (TKIs), such as gefitinib (Iressa) and erlotinib (Tarceva), are limited due to the development of resistance, which contributes to treatment failure and cancer-related mortality. The aim of this study was to elucidate mechanistic insight into cellular perturbations that accompany acquired gefitinib resistance in lung cancer cells. Several lung adenocarcinoma (LAD) cell lines were screened to characterize epidermal growth factor receptor (EGFR) expression and mutation profile...
April 3, 2015: Journal of Biological Chemistry
Takeshi Nakahara, Yoichi Moroi, Koichi Takayama, Eriko Itoh, Makiko Kido-Nakahara, Yoichi Nakanishi, Masutaka Furue
BACKGROUND: It has recently been shown that patients treated with epidermal growth factor receptor (EGFR) inhibitors often develop various cutaneous adverse events. While the pathogenesis underlying these events remains unclear, the relationship between skin toxicity induced by EGFR inhibitors and the sebaceous glands that express EGFR has been previously reported. OBJECTIVES: The primary aim of this study was to determine the relationship between cutaneous sebum levels and acneiform rash, a typical skin toxicity of EGFR inhibitors, by measuring the sebum levels before and after EGFR inhibitor treatment...
2015: OncoTargets and Therapy
Youngjoo Kim, Mihaela Apetri, BeiBei Luo, Jeffrey E Settleman, Karen S Anderson
UNLABELLED: Constitutive activation of EGFR due to overexpression or mutation in tumor cells leads to dysregulated downstream cellular signaling pathways. Therefore, EGFR as well as its downstream effectors have been identified as important therapeutic targets. The FDA-approved small-molecule inhibitors of EGFR, gefitinib (Iressa) and erlotinib (Tarceva), are clinically effective in a subset of patients with non-small cell lung cancer (NSCLC) whose tumors harbor activating mutations within the kinase domain of EGFR...
April 2015: Molecular Cancer Research: MCR
Anthony B Daniels, Matt L Miller, Amy Kotecha, David H Abramson
PURPOSE: To report the case of a never-smoker patient whose initial presentation of metastatic nonsmall cell lung carcinoma was with uveal metastasis, which had a dramatic response to targeted biologic therapy with erlotinib (Tarceva) after failing conventional chemotherapy. METHODS: Case report. A 43-year-old man with uveal metastasis from nonsmall cell lung adenocarcinoma. RESULTS: After failing conventional chemotherapy with carboplatin and taxol, with continued documented rapid growth of the uveal metastasis, treatment was initiated with the targeted biologic agent, erlotinib, which is a protein tyrosine kinase inhibitor of the epidermal growth factor receptor(EGFR)...
2010: Retinal Cases & Brief Reports
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