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https://www.readbyqxmd.com/read/28507280/molecular-dissection-of-effector-mechanisms-of-ras-mediated-resistance-to-anti-egfr-antibody-therapy
#1
Stefan Kasper, Henning Reis, Sophie Ziegler, Silke Nothdurft, Andre Mueller, Moritz Goetz, Marcel Wiesweg, Jeannette Phasue, Saskia Ting, Sarah Wieczorek, Anna Even, Karl Worm, Michael Pogorzelski, Sandra Breitenbuecher, Johannes Meiler, Andreas Paul, Tanja Trarbach, Kurt Werner Schmid, Frank Breitenbuecher, Martin Schuler
Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR), cetuximab and panitumumab, are a mainstay of metastatic colorectal cancer (mCRC) treatment. However, a significant number of patients suffer from primary or acquired resistance. RAS mutations are negative predictors of clinical efficacy of anti-EGFR antibodies in patients with mCRC. Oncogenic RAS activates the MAPK and PI3K/AKT pathways, which are considered the main effectors of resistance. However, the relative impact of these pathways in RAS-mutant CRC is less defined...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28490902/patient-and-physician-preferences-for-anticancer-drugs-for-the-treatment-of-metastatic-colorectal-cancer-a-discrete-choice-experiment
#2
Juan Marcos González, Sarika Ogale, Robert Morlock, Joshua Posner, Brett Hauber, Nicolas Sommer, Axel Grothey
OBJECTIVE: Many publications describe preferences for colorectal cancer (CRC) screening; however, few studies elicited preferences for anticancer-drug treatment for metastatic CRC (mCRC). This study was designed to elicit preferences and risk tolerance among patients and oncologists in the USA for anticancer drugs to treat mCRC. MATERIALS AND METHODS: Patients aged 18 years or older with a self-reported diagnosis of mCRC and board-certified (or equivalent) oncologists who had treated patients with mCRC were recruited by two survey research companies from existing online patient panels in the USA...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28475639/establishment-of-human-metastatic-colorectal-cancer-model-in-rabbit-liver-a-pilot-study
#3
Veronica Prieto, Johannes M Ludwig, Alton B Farris, Ganji Purnachandra Nagaraju, Taoreed O Lawal, Bassel El-Rayes, Hyun S Kim
RATIONALE AND OBJECTIVES: To develop a human metastatic colorectal cancer (mCRC) model in a rabbit liver. MATERIALS AND METHODS: Immunosuppression in 4 adult New Zealand White rabbits weighing 3.5 to 4.5 kg was induced with daily subcutaneous injection of 15 mg/kg Cyclosporine A (CsA). On day 3 open mini-laparotomy was performed and 0.2 ml (1.8x105 cells) suspension of HCT-116 and HT-29 human CRC cells were injected into the left and right medial lobe respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28473715/rationally-co-targeting-divergent-pathways-in-kras-wild-type-colorectal-cancers-by-canscript-technology-reveals-tumor-dependence-on-notch-and-erbb2
#4
Nilesh Brijwani, Misti Jain, Muthu Dhandapani, Farrah Zahed, Pragnashree Mukhopadhyay, Manjusha Biswas, Deepak Khatri, Vinod D Radhakrishna, Biswanath Majumder, Padhma Radhakrishnan, Saravanan Thiyagarajan
KRAS mutation status can distinguish between metastatic colorectal carcinoma (mCRC) patients who may benefit from therapies that target the epidermal growth factor receptor (EGFR), such as cetuximab. However, patients whose tumors harbor mutant KRAS (codons 12/13, 61 and 146) are often excluded from EGFR-targeted regimens, while other patients with wild type KRAS will sometimes respond favorably to these same drugs. These conflicting observations suggest that a more robust approach to individualize therapy may enable greater frequency of positive clinical outcome for mCRC patients...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28468669/kras-mutation-analysis-of-single-circulating-tumor-cells-from-patients-with-metastatic-colorectal-cancer
#5
Yuurin Kondo, Kazuhiko Hayashi, Kazuyuki Kawakami, Yukari Miwa, Hiroshi Hayashi, Masakazu Yamamoto
BACKGROUND: The molecular profiles of tumors may inform the selection of appropriate targeted therapies. Circulating tumor cells (CTCs) reflect the real-time status of tumor genotypes. CTCs exhibit high genetic heterogeneity within a patient; accordingly, the analysis of individual CTCs, including their heterogeneity, may enable more precise treatments. We analyzed KRAS mutations in single CTCs from patients with metastatic colorectal cancer (mCRC) using a new single-cell picking system...
May 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28455957/ras-testing-and-cetuximab-treatment-for-metastatic-colorectal-cancer-a-cost-effectiveness-analysis-in-a-setting-with-limited-health-resources
#6
Bin Wu, Yuan Yao, Ke Zhang, Xuezhen Ma
PURPOSE: To test the cost-effectiveness of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment in patients with metastatic colorectal cancer (mCRC) from a Chinese medical insurance perspective. RESULTS: Baseline analysis showed that the addition of cetuximab increased quality-adjusted life-years (QALYs) by 0.63, an increase of $17,086 relative to FOLFIRI chemotherapy, resulting in an incremental cost-effectiveness ratio (ICER) of $27,145/QALY...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453695/genetic-variants-of-dna-repair-related-genes-predict-efficacy-of-tas-102-in-patients-with-refractory-metastatic-colorectal-cancer
#7
M Suenaga, M Schirripa, S Cao, W Zhang, D Yang, S Murgioni, D Rossini, F Marmorino, A Mennitto, Y Ning, S Okazaki, M D Berger, Y Miyamoto, R Gopez, A Barzi, T Yamaguchi, F Loupakis, H-J Lenz
Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28451414/response-to-regorafenib-at-an-initial-dose-of-120-mg-as-salvage-therapy-for-metastatic-colorectal-cancer
#8
Hiroshi Osawa
Regorafenib (Reg) is an oral multikinase inhibitor that has achieved improved overall survival in patients with metastatic colorectal cancer (mCRC) in the salvage therapy setting. However, Reg is difficult to manage and determine the optimal dose due to adverse events (AEs). The objective of this study was to retrospectively evaluate the clinical benefit and determine the optimal dose of Reg in mCRC patients. A total of 20 mCRC patients were enrolled in this retrospective study. Initially, 8 patients who received a starting dose of 160 mg Reg (160 mg group) once a day were evaluated; however, they were unable to continue with the initial dose of 160 mg due to grade 3 adverse events (AEs), such as hand-foot skin reaction (HFSR) and small intestinal hemorrhage...
March 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28449055/primary-tumor-sidedness-has-an-impact-on-prognosis-and-treatment-outcome-in-metastatic-colorectal-cancer-results-from-two-randomized-first-line-panitumumab-studies
#9
N Boeckx, R Koukakis, K Op de Beeck, C Rolfo, G Van Camp, S Siena, J Tabernero, J-Y Douillard, T André, M Peeters
Background: : Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors. Material and methods: Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients...
April 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28447565/risk-factors-for-brain-metastases-in-patients-with-metastatic-colorectal-cancer
#10
Troels Dreier Christensen, Jesper Andreas Palshof, Finn Ole Larsen, Estrid Høgdall, Tim Svenstrup Poulsen, Per Pfeiffer, Benny Vittrup Jensen, Mette Karen Yilmaz, Ib Jarle Christensen, Dorte Nielsen
BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients. MATERIAL AND METHODS: We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment...
May 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28446505/clinical-features-and-outcomes-of-patients-with-colorectal-cancers-harboring-nras-mutations
#11
Andrea Cercek, Maria Ignez Braghiroli, Joanne F Chou, Jaclyn F Hechtman, Nancy E Kemeny, Leonard Saltz, Marinela Capanu, Rona Yaeger
Purpose: NRAS mutations are now routinely included in RAS testing prior to EGFR (epidermal growth factor receptor) inhibitor therapy for metastatic colorectal cancer (mCRC).  The clinical implications of NRAS mutation beyond lack of response to anti-EGFR therapy, however, are not known.  We undertook this study to determine the clinical features and treatment outcomes of patients with NRAS mutant mCRC.<br />Experimental Design: We reviewed clinical characteristics, concurrent mutations, and outcomes for all mCRC cases with NRAS mutations undergoing standard genotyping at our institution from 2008-2015...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28438615/clinicopathological-immunohistochemical-and-mutational-analyses-of-pulmonary-enteric-adenocarcinoma-usefulness-of-satb2-and-%C3%AE-catenin-immunostaining-for-differentiation-from-metastatic-colorectal-carcinoma
#12
Jun Matsushima, Takuya Yazawa, Masaki Suzuki, Yoko Takahashi, Satoshi Ota, Takahiro Nakajima, Ichiro Yoshino, Tomoyuki Yokose, Toru Inoue, Kunimitsu Kawahara, Yukio Nakatani
Pulmonary enteric adenocarcinoma (PEA) is a rare variant of pulmonary adenocarcinoma; it is sometimes difficult to discriminate between PEA and metastatic colorectal carcinoma (MCRC) because of their morphological and immunohistochemical resemblance. Here, we conducted clinicopathological, immunohistochemical, and mutational analyses of PEA with special focus on its differentiation from MCRC. We comparatively analyzed eight surgically resected PEA tumors (7 patients) and 20 cases of MCRC. Patients were aged 43-77years (average age, 64...
April 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28435294/patient-considerations-in-metastatic-colorectal-cancer-role-of-panitumumab
#13
REVIEW
Jane E Rogers
Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies, including colorectal cancer (CRC), making EGFR an attractive treatment option. Panitumumab and cetuximab, monoclonal antibodies (mAbs) directed at EGFR, are both currently utilized in the management of metastatic CRC (mCRC). Through the development of these agents in mCRC, key issues surrounding each mAbs use have been revealed. These key issues include negative patient outcome avoidance when determining use, the economic burden with high-cost medication, predictive biomarkers, tumor location, patient geographic location, patient quality of life, and the prevention of debilitating adverse effects...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28433602/folfoxiri-regimen-for-metastatic-colorectal-cancer-a-systematic-review-and-meta-analysis
#14
Frederico Leal, Fernanda Proa Ferreira, Andre Deeke Sasse
INTRODUCTION: Cytotoxic chemotherapy is the mainstay treatment for metastatic colorectal cancer (mCRC). Fluoropyrimidines, oxaliplatin, and irinotecan are the most active drugs; however, their optimal sequencing has not yet been established. Some evidence has shown that upfront treatment with 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI regimen) can improve outcomes for patients with mCRC. MATERIALS AND METHODS: We performed a systematic search in electronic databases...
March 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28433601/volumetric-versus-unidimensional-measures-of-metastatic-colorectal-cancer-in-assessing-disease-response
#15
Meghan G Lubner, Nicholas Stabo, Sam J Lubner, Alejandro Munoz Del Rio, Chihwa Song, Perry J Pickhardt
INTRODUCTION: The purpose of this study was to compare unidimensional (1D/linear) and volumetric (3D) measures of metastatic colorectal cancer (mCRC) at computed tomography (CT) for predicting clinical outcome. PATIENTS AND METHODS: Analysis of CT images in 105 patients (mean age, 59 years; range, 25-81 years; 45 women, 60 men) receiving treatment for mCRC was performed. Both unidimensional and volumetric measures were obtained on index lesions at 3 time points (baseline/midpoint/post-therapy; mean interval, 4...
March 27, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28432610/left-versus-right-does-location-matter-for-refractory-metastatic-colorectal-cancer-patients-in-phase-1-clinical-trials
#16
Sukeshi Patel Arora, Norma S Ketchum, Joel Michalek, Jonathon Gelfond, Devalingam Mahalingam
PURPOSE: Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies. METHODS: A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012...
April 22, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28430643/lymph-node-status-as-a-prognostic-factor-after-palliative-resection-of-primary-tumor-for-patients-with-metastatic-colorectal-cancer
#17
Qingguo Li, Changjian Wang, Yaqi Li, Xinxiang Li, Ye Xu, Guoxiang Cai, Peng Lian, Sanjun Cai
Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The study aimed to explore the prognostic value of LN status after palliative resection of primary tumor for patients with metastatic colorectal cancer (mCRC). We combined analyses of mCRC patients in Surveillance, Epidemiology and End Results (SEER) database and Fudan University Shanghai Cancer Center (FUSCC).A total of 17,553 patients with mCRC were identified in SEER database...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430159/efficacy-of-low-molecular-weight-fucoidan-as-a-supplemental-therapy-in-metastatic-colorectal-cancer-patients-a-double-blind-randomized-controlled-trial
#18
Hsiang-Lin Tsai, Chi-Jung Tai, Ching-Wen Huang, Fang-Rong Chang, Jaw-Yuan Wang
BACKGROUND: Low-molecular-weight fucoidan (LMF) is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical evidence for LMF use is relatively weak. This study aimed to evaluate the efficacy of LMF as a supplemental therapy to chemo-target agents in metastatic colorectal cancer (mCRC) patients. METHODS: We conducted a prospective, randomized, double-blind, controlled trial to evaluate the efficacy of LMF as a supplemental therapy to chemotarget agents in patients with metastatic colorectal cancer (mCRC)...
April 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28428512/-change-of-blood-neutrophil-to-lymphocyte-ratio-predicts-survival-in-patients-with-metastatic-colorectal-cancer
#19
Katsuki Muneoka, Yoshio Shirai, Masataka Sasaki, Jun Sakata, Junkichi Kanda, Hiroyuki Wakabayashi, Toshifumi Wakai
AIM: The impact of neutrophil-to-lymphocyte ratio(NLR)changes on the outcome of chemotherapy for metastatic colorectalcancer (mCRC)was analyzed retrospectively. METHODOLOGY: Twenty seven patients with unresectable mCRC were administered chemotherapy from January 2005 to December 2014 at the Niitsu Medical Center Hospital. The NLR was calculated from complete blood counts obtained prior to the administration of chemotherapy and at the best response. We defined the period with NLR≤2...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28426267/a-phase-2-trial-of-single-agent-axitinib-as-maintenance-therapy-following-first-line-treatment-with-modified-folfox-bevacizumab-in-patients-with-metastatic-colorectal-cancer
#20
Johanna C Bendell, Mathew Joseph, Kirk Barnes, Mark Mainwaring, Dianna Shipley, Chandra Reddy, Laura Blakely, Ronald Blachly, Cassie M Lane, Chris Earwood, Michel Kuzur
This phase-2 trial evaluated the efficacy of axitinib as maintenance therapy for patients with metastatic colorectal cancer (mCRC) following first-line treatment with FOLFOX/bevacizumab. Patients with mCRC received mFOLFOX/bevacizumab followed by axitinib maintenance after four cycles. The primary endpoint was progression-free survival (PFS). Seventy patients were enrolled. Common treatment-related toxicities were fatigue, nausea, diarrhea, and peripheral neuropathy during FOLFOX/bevacizumab treatment; and fatigue, hypertension, diarrhea, and peripheral neuropathy during axitinib treatment...
April 20, 2017: Cancer Investigation
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