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Jenny F Seligmann, Faye Elliott, Susan D Richman, Bart Jacobs, Gemma Hemmings, Sarah Brown, Jennifer H Barrett, Sabine Tejpar, Philip Quirke, Matthew T Seymour
Importance: RAS wild-type (wt) status is necessary but not sufficient for response to anti-epidermal growth factor receptor (EGFR) agents in advanced colorectal cancer (aCRC). RNA expression of EGFR ligands epiregulin (EREG) and amphiregulin (AREG) may correlate with EGFR-targeted therapy efficacy in aCRC, so may represent a much-needed additional predictive marker for these drugs. Objective: To examine a novel ligand model in a randomized clinical trial of panitumumab, irinotecan, and ciclosporin in colorectal cancer (PICCOLO) with with the a priori hypothesis that high tumor expression of either AREG or EREG would predict panitumumab therapy benefit in RAS-wt patients; and low expression, lack of efficacy...
February 11, 2016: JAMA Oncology
Lorenzo Antonuzzo, Elisa Giommoni, Davide Pastorelli, Tiziana Latiano, Ida Pavese, Domenico Azzarello, Michele Aieta, Ilaria Pastina, Francesca Di Fabio, Alessandro Bertolini, Domenico Cristiano Corsi, Selene Mogavero, Valentina Angelini, Mario Pazzagli, Francesco Di Costanzo
AIM: To confirm the efficacy and safety of bevacizumab/XELOX combination for the treatment of locally advanced or metastatic colorectal cancer (CRC) in Italy. METHODS: This multicentric, prospective, open-label study included patients with CRC previously untreated with chemotherapy. Patients were administered bevacizumab in combination with XELOX. The primary efficacy end-point was progression-free survival (PFS). Secondary end-points included time to overall response (TOR), duration of response (DOR), time to treatment failure (TTF) and overall survival (OS)...
June 21, 2015: World Journal of Gastroenterology: WJG
Amber Dahlin, Augusto Litonjua, John J Lima, Mayumi Tamari, Michiaki Kubo, Charles G Irvin, Stephen P Peters, Kelan G Tantisira
BACKGROUND: Genome-wide association study (GWAS) is a powerful tool to identify novel pharmacogenetic single nucleotide polymorphisms (SNPs). Leukotriene receptor antagonists (LTRAs) are a major class of asthma medications, and genetic factors contribute to variable responses to these drugs. We used GWAS to identify novel SNPs associated with the response to the LTRA, montelukast, in asthmatics. METHODS: Using genome-wide genotype and phenotypic data available from American Lung Association - Asthma Clinical Research Center (ALA-ACRC) cohorts, we evaluated 8-week change in FEV1 related to montelukast administration in a discovery population of 133 asthmatics...
2015: PloS One
Judith R Kroep, Erik van Werkhoven, Marco Polee, Cees J van Groeningen, Aart Beeker, Frans Erdkamp, Nir Weijl, Aart van Bochove, Zoran Erjavec, Ellen Kapiteijn, Anne M Stiggelbout, Hans W R Nortier, Hans Gelderblom
BACKGROUND: Prospective data on chemotherapy for (frail) elderly patients with advanced colorectal cancer (aCRC) are scant. UFT/leucovorin might be as effective as and less toxic than capecitabine. We firstly randomized both agents in patients >65 years with aCRC not amenable to receive combination chemotherapy. PATIENTS AND METHODS: Patients were randomised between first-line oral UFT/leucovorin and capecitabine in a Dutch multicentre trial. Primarily, efficacy and toxicity were determined...
July 2015: Journal of Geriatric Oncology
Hui Xu, Huiying Sun, Haiyuan Zhang, Jiawei Liu, Fangfang Fan, Yilan Li, Xuelian Ning, Yue Sun, Shaochun Dai, Baogang Liu, Min Gao, Songbin Fu, Chunshui Zhou
BACKGROUND: Lung cancer is emerging rapidly as the leading death cause in Chinese cancer patients. The causal factors for Chinese lung cancer development remain largely unclear. Here we employed an shRNA library-based loss-of-function screen in a genome-wide and unbiased manner to interrogate potential tumor suppressor candidates in the immortalized human lung epithelial cell line BEAS-2B. METHODS/RESULTS: Soft agar assays were conducted for screening BEAS-2B cells infected with the retroviral shRNA library with the acquired feature of anchorage-independent growth, large (>0...
2015: PloS One
Oriana Ciani, Marc Buyse, Ruth Garside, Jaime Peters, Everardo D Saad, Ken Stein, Rod S Taylor
OBJECTIVES: To quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). STUDY DESIGN AND SETTING: We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form...
July 2015: Journal of Clinical Epidemiology
Alain Hendlisz, Amélie Deleporte, Caroline Vandeputte, Nicolas Charette, Marianne Paesmans, Thomas Guiot, Camilo Garcia, Patrick Flamen
INTRODUCTION: Regorafenib was recently approved for patients with pretreated advanced colorectal cancer (aCRC), despite a moderate improvement of the patients' outcome, and significant toxicities. Based on previous studies showing that early fluorodeoxyglucose-positron emission tomography (FDG-PET)-based metabolic response assessment (MRA) might adequately select patients unlikely to benefit from treatment, the RegARd-C trial uses early MRA to identify likely non-responders to regorafenib in a population of patients with aCRC and guide a comprehensive evaluation of genomic and epigenetic determinants of resistance to treatment...
2015: BMJ Open
Matthew G Krebs, Andrew G Renehan, Alison Backen, Simon Gollins, Ian Chau, Jurjees Hasan, Juan W Valle, Karen Morris, Janette Beech, Linda Ashcroft, Mark P Saunders, Caroline Dive
BACKGROUND: Multidrug regimens are active against advanced colorectal cancer (ACRC). However, the increased toxicity requires the use of biomarkers to select the patients who will derive the most benefit. We assessed circulating tumor cells (CTCs) as a prognostic biomarker in patients treated with a 4-drug regimen. PATIENTS AND METHODS: A single-arm phase II trial (Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted-therapy [eSCOUT]) was undertaken in patients with previously untreated KRAS wild-type ACRC using a regimen of irinotecan, oxaliplatin, and tegafur-uracil with leucovorin and cetuximab...
June 2015: Clinical Colorectal Cancer
Jiaxiang Ye, Jiawei Chen, Lianying Ge, Aiqun Liu, Shaozhang Zhou
Objectives. The aim of our study was to compare the efficacy and safety of S-1-based therapy (SBT) versus 5-fluorouracil-based therapy (FBT) for advanced colorectal cancer (ACRC). Methods. A meta-analysis of all eligible randomized controlled trials (RCTs) was performed using RevMan 5.1.0 software. Results. A total of 1625 patients from twelve RCTs including 820 patients in the SBT group and 805 patients in the FBT group were available for analysis. The meta-analysis of overall survival (hazards ratio HR = 0...
2014: Gastroenterology Research and Practice
Sharlene Gill, Scot Dowden, Bruce Colwell, Loretta L Collins, Scott Berry
Colorectal cancer (CRC) is the third most commonly diagnosed cancer among males and second among females worldwide. The treatment landscape for advanced CRC (aCRC) is rapidly evolving and there are now a number of randomized trials assessing treatment of aCRC beyond first-line, prompting important questions about how to optimize therapy and maximize benefit. The availability of targeted agents has increased the complexity of post-progression treatment of aCRC. Targeted biological agents with varying modes of action are now approved for use in second-line and beyond, including the VEGF-inhibitors bevacizumab and aflibercept, the VEGFR/multikinase-inhibitor regorafenib, and the EGFR-inhibitors cetuximab and panitumumab...
December 2014: Cancer Treatment Reviews
Yoshiki Kimura, Hiroshi Matsumoto, Motoyasu Oosawa, Minoru Fujita, Ken-Ichi Tarumi, Tomoari Kamada, Akiko Shiotani, Ken Haruma
We evaluated the relationship between colorectal neoplasms and visceral obesity using computed tomographic colonography and adipocytokine levels. We included 123 patients and classified them into four groups as per computed tomographic colonography: no lesion (NL; n=40), adenomatous polyp (polyp; n=41), early colorectal cancer (eCRC; n=21), and advanced CRC (aCRC; n=21). We also measured the patients' serum metabolic markers and adipocytokine levels. The visceral adiposity index in the polyp and eCRC groups was significantly higher than that in the NL group...
November 2014: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
Shiro Kibe, Shigeru Yutani, Satoru Motoyama, Takanobu Nomura, Natsuki Tanaka, Akihiko Kawahara, Tomohiko Yamaguchi, Satoko Matsueda, Nobukazu Komatsu, Masatomo Miura, Yudai Hinai, Satoshi Hattori, Akira Yamada, Masayoshi Kage, Kyogo Itoh, Yoshito Akagi, Tetsuro Sasada
The prognosis of advanced colorectal cancer (aCRC) remains poor, and development of new therapeutic approaches, including immunotherapy, is needed urgently. Herein we report on our phase II study of personalized peptide vaccination (PPV) in 60 previously treated patients with aCRC, who had failed at least one regimen of standard chemotherapy and/or targeted therapy. For PPV, a maximum of four HLA-matched peptides were individually selected from a pool of 31 different peptide candidates based on preexisting host immunity, and administered subcutaneously without severe adverse events...
December 2014: Cancer Immunology Research
Jia-Xiang Ye, Ai-Qun Liu, Lian-Ying Ge, Shao-Zhang Zhou, Zhong-Guo Liang
The aim of the present analysis was to compare the efficacy and safety profile of S-1-based chemotherapy (SBCT) versus capecitabine-based chemotherapy (CBCT) for advanced gastric cancer (AGC) and advanced colorectal cancer (ACRC). A meta-analysis was performed, which included eligible randomized controlled trials (RCTs) that were identified using RevMan 5.1.0 software. A total of 1,064 patients from 11 RCTs, comprising of 527 patients in the SBCT group and 537 patients in the CBCT group, were included in the analysis...
May 2014: Experimental and Therapeutic Medicine
Menghua Chen, Brian H May, Iris W Zhou, Charlie C L Xue, Anthony L Zhang
This systematic review evaluates the clinical evidence for the addition of herbal medicines (HMs) to FOLFOX 4 for advanced colorectal cancer (ACRC) in terms of tumor response rate (tRR), survival, quality of life and reduction in adverse events (AEs). Seven electronic databases were searched for randomized controlled trials (RCTs) of FOLFOX4 combined with HMs compared to FOLFOX4 alone. Outcome data for 13 randomized controlled trials were analysed using Review Manager 5.1. Risk of bias for objective outcomes including tumor response and survival was judged as low...
July 2014: Phytotherapy Research: PTR
Charlotte Lemech, Hendrik-Tobias Arkenau
The growing number of therapeutic agents and known molecular targets in oncology makes the study and clinical use of biomarkers imperative for improving response and survival, reducing toxicity and ensuring economic sustainability. Colorectal cancer, among others, is at the forefront of development of predictive and prognostic biomarkers; however, the difficulty lies in translating potential biomarkers garnered from retrospective analyses in small numbers of patients to generalizable and affordable biomarkers used worldwide...
2011: Cancers
Jennifer W McCallister, Janet T Holbrook, Christine Y Wei, Jonathan P Parsons, Cathy G Benninger, Anne E Dixon, Lynn B Gerald, John G Mastronarde
OBJECTIVE: Important differences between men and women with asthma have been demonstrated, with women describing more symptoms and worse asthma-related quality of life (QOL) despite having similar or better pulmonary function. While current guidelines focus heavily on assessing asthma control, they lack information about whether sex-specific approaches to asthma assessment should be considered. We sought to determine if sex differences in asthma control or symptom profiles exist in the well-characterized population of participants in the American Lung Association Asthma Clinical Research Centers (ALA-ACRC) trials...
October 2013: Respiratory Medicine
Shawnagay Nestheide, Julia A Bridge, Michael Barnes, Robert Frayer, Janos Sumegi
BACKGROUND: Ewing sarcoma (ES), a highly aggressive tumor of children and young adults, is characterized most commonly by an 11;22 chromosomal translocation that fuses EWSR1 located at 22q12 with FLI1, coding for a member of the ETS family of transcription factors. Although genetic changes in ES have been extensively researched, our understanding of the role of epigenetic modifications in this neoplasm is limited. PROCEDURE: In an effort to improve our knowledge in the role of epigenetic changes in ES we evaluated the in vitro antineoplastic effect of the DNA methyltransferase inhibitor 5-Aza-deoxycytidine (5-Aza-dC) and identified epigenetically silenced genes by pharmacologic unmasking of DNA methylation coupled with genome-wide expression profiling...
September 2013: Pediatric Blood & Cancer
Jordi Codony-Servat, Xabier Garcia-Albeniz, Carles Pericay, Vicente Alonso, Pilar Escudero, Carlos Fernández-Martos, Rosa Gallego, Anna Martínez-Cardús, Eva Martinez-Balibrea, Joan Maurel
The FAS/FASL system, comprising membrane-bound (mFAS and mFASL) and soluble forms (sFAS and sFASL), has been related to apoptosis driven by chemotherapy administration. In vitro experiments show chemotherapy upregulating membrane-bound forms, leading to an increase of receptor availability (at 24-72 h) and favoring apoptosis. The regulatory effect of chemotherapy on sFAS in patients has never been explored prospectively in advanced colorectal cancer (ACRC). We performed a pharmacodynamic study to address sFAS/sFASL variation...
March 2013: Medical Oncology
A Madi, D Fisher, R H Wilson, R A Adams, A M Meade, S L Kenny, L L Nichols, M T Seymour, H Wasan, R Kaplan, T S Maughan
BACKGROUND: COIN compared first-line continuous chemotherapy with the same chemotherapy given intermittently or with cetuximab in advanced colorectal cancer (aCRC). METHODS: Choice between oxaliplatin/capecitabine (OxCap) and oxaliplatin/leucovorin (LV)/infusional 5-FU (OxFU) was by physician and patient choice and switching regimen was allowed. We compared OxCap with OxFU and OxCap+cetuximab with OxFU+cetuximab retrospectively in patients and examined efficacy, toxicity profiles and the effect of mild renal impairment...
September 25, 2012: British Journal of Cancer
Gui-Fang Guo, Wen-Qi Jiang, Bei Zhang, Yu-Chen Cai, Rui-Hua Xu, Xu-Xian Chen, Fang Wang, Liang-Ping Xia
AIM: To investigate the utility of Beclin-1 and LC3, two autophagy-related proteins, in predicting the cetuximab efficacy in advanced colorectal cancer (ACRC). METHODS: The data of 85 patients with ACRC treated at the Sun Yat-sen University Cancer Center from March 1, 2005 to December 31, 2008 were studied, including 45 cases treated with cetuximab-containing chemotherapy and 40 cases treated with non-cetuximab-containing chemotherapy. Beclin-1 and LC3 expression was evaluated by immunohistochemistry, and KRAS status was evaluated by polymerase chain reaction...
November 21, 2011: World Journal of Gastroenterology: WJG
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