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https://www.readbyqxmd.com/read/28099361/the-cardiotoxicity-of-cetuximab-as-single-therapy-in-chinese-chemotherapy-refractory-metastatic-colorectal-cancer-patients
#1
Xue-Miao Tang, Hao Chen, Yu Liu, Bin-Lian Huang, Xiu-Quan Zhang, Jian-Mei Yuan, Xia He
The cardiac safety of cetuximab, particularly as single approach, has not been investigated extensively. This trial was designed to evaluate the cardiac safety of cetuximab as salvage monotherapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC) patients.Cetuximab was administrated at an initial dose of 400 mg/mon day 1 (week 1), followed by a maintenance dose of 250 mg/m on day 1 of each 7-day cycle. Electrocardiograph (ECG), routine laboratory tests, and troponin I (TNI) Ultra were performed at baseline, during, and after the cetuximab therapy...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28094264/first-line-therapy-for-mcrc-the-influence-of-primary-tumour-location-on-the-therapeutic-algorithm
#2
Chiara Cremolini, Carlotta Antoniotti, Roberto Moretto, Gianluca Masi, Alfredo Falcone
No abstract text is available yet for this article.
January 17, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28088467/stat3-signaling-mediates-tumour-resistance-to-egfr-targeted-therapeutics
#3
Ahmad A Zulkifli, Fiona H Tan, Tracy L Putoczki, Stanley S Stylli, Rodney B Luwor
Several EGFR inhibitors are currently undergoing clinical assessment or are approved for the clinical management of patients with varying tumour types. However, treatment often results in a lack of response in many patients. The majority of patients that initially respond eventually present with tumours that display acquired resistance to the original therapy. A large number of receptor tyrosine and intracellular kinases have been implicated in driving signaling that mediates this tumour resistance to anti-EGFR targeted therapy, and in a few cases these discoveries have led to overall changes in prospective tumour screening and clinical practice (K-RAS in mCRC and EGFR T790M in NSCLC)...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28081548/serum-ldh-predicts-benefit-from-bevacizumab-beyond-progression-in-metastatic-colorectal-cancer
#4
Federica Marmorino, Lisa Salvatore, Cecilia Barbara, Giacomo Allegrini, Lorenzo Antonuzzo, Gianluca Masi, Fotios Loupakis, Beatrice Borelli, Silvana Chiara, Maria Chiara Banzi, Emanuela Miraglio, Domenico Amoroso, Francesco Dargenio, Andrea Bonetti, Angelo Martignetti, Myriam Paris, Daniela Tomcikova, Luca Boni, Alfredo Falcone, Chiara Cremolini
BACKGROUND: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. METHODS: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28063788/response-to-chemotherapy-and-prognosis-in-metastatic-colorectal-cancer-with-dna-deficient-mismatch-repair
#5
Alexandra Khichfy Alex, Sheila Siqueira, Renata Coudry, Juliana Santos, Michel Alves, Paulo M Hoff, Rachel P Riechelmann
BACKGROUND: DNA deficient mismatch repair (dMMR) genes are associated with microsatellite instability and good prognosis in early-stage colorectal cancer (CRC). However dMMR is rare in metastatic CRC (mCRC) and little is known about its influence on treatment response rate (RR). The primary objective of this study was to compare the RR of patients with mCRC according to dMMR status. METHODS: This was a retrospective study that compared the RR by Response Evaluation Criteria In Solid Tumors 1...
November 26, 2016: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28053287/clinical-parameters-to-guide-decision-making-in-elderly-metastatic-colorectal-cancer-patients-treated-with-intensive-cytotoxic-and-anti-angiogenic-therapy
#6
Gemma Bruera, Antonio Russo, Antonio Galvano, Sergio Rizzo, Enrico Ricevuto
INTRODUCTION: Bevacizumab addiction to triplet chemotherapy, according to FIr-B/FOx schedule, as first-line treatment in young-elderly metastatic colorectal CANCER (MCRC) patients may be more effective. Tailored treatments show worse clinical outcome in unfit patients. METHODS: Elderly patients were clinically evaluated according to age and comorbidity (Cumulative Illness Rating Scale) to select FIr-B/FOx regimen in fit or tailored treatments in unfit elderly. Limiting toxicity syndromes (LTS) were evaluated...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28040715/prolonged-response-to-her2-directed-therapy-in-a-patient-with-her2-amplified-rapidly-progressive-metastatic-colorectal-cancer
#7
Aparna Parikh, Chloe Atreya, W Michael Korn, Alan P Venook
HER2 gene amplifications and activating mutations in the HER2 receptor tyrosine kinase are present in 4% of metastatic colorectal cancers (mCRCs). HER2-targeted therapy is not standard of care, although preclinical and clinical data suggest that patients with HER2 amplifications and/or HER2-activating mutations may benefit from HER2-directed therapy. HER2 amplifications and activating mutations have also been implicated in resistance to anti-epidermal growth factor receptor-based therapy. This report describes a patient with KRAS, NRAS, and BRAF wild-type mCRC who experienced disease progression on first-line treatment with FOLFIRI and cetuximab after only 5 months, and subsequently experienced progression on second-line treatment with capecitabine and oxaliplatin plus bevacizumab after 2 months with significant functional decline...
January 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28032593/the-impact-of-co-expression-of-wild-type-egfr-and-its-ligands-determined-by-immunohistochemistry-for-response-to-treatment-with-cetuximab-in-patients-with-metastatic-colorectal-cancer
#8
Said Khelwatty, Sharadah Essapen, Izhar Bagwan, Margaret Green, Alan Seddon, Helmout Modjtahedi
Anti-EGFR mAbs cetuximab and panitumumab are routinely used for the treatment of patients with KRAS-wild type metastatic colorectal cancer (mCRC). However, in some patients their efficacy remains modest and with no clear association between the EGFR protein expression determined by PharmDx™ kit, and response to anti-EGFR therapies. Therefore, we investigated the relative expression and predictive value of wild-type EGFR (wtEGFR), mutated EGFRvIII and EGFR ligand proteins in mCRC patients treated with cetuximab...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029553/somatic-mutation-detection-using-various-targeted-detection-assays-in-paired-samples-of-circulating-tumor-dna-primary-tumor-and-metastases-from-patients-undergoing-resection-of-colorectal-liver-metastases
#9
Nick Beije, Jean C Helmijr, Marjolein J A Weerts, Corine M Beaufort, Matthew Wiggin, Andre Marziali, Cornelis Verhoef, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens
Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR)...
October 10, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28025930/cost-effectiveness-of-treatment-sequences-of-chemotherapies-and-targeted-biologics-for-elderly-metastatic-colorectal-cancer-patients
#10
Rohan C Parikh, Xianglin L Du, Morgan O Robert, David R Lairson
BACKGROUND: Treatment patterns for metastatic colorectal cancer (mCRC) patients have changed considerably over the last decade with the introduction of new chemotherapies and targeted biologics. These treatments are often administered in various sequences with limited evidence regarding their cost-effectiveness. OBJECTIVE: To conduct a pharmacoeconomic evaluation of commonly administered treatment sequences among elderly mCRC patients. METHODS: A probabilistic discrete event simulation model assuming Weibull distribution was developed to evaluate the cost-effectiveness of the following common treatment sequences: (a) first-line oxaliplatin/irinotecan followed by second-line oxaliplatin/irinotecan + bevacizumab (OI-OIB); (b) first-line oxaliplatin/irinotecan + bevacizumab followed by second-line oxaliplatin/irinotecan + bevacizumab (OIB-OIB); (c) OI-OIB followed by a third-line targeted biologic (OI-OIB-TB); and (d) OIB-OIB followed by a third-line targeted biologic (OIB-OIB-TB)...
January 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28024424/the-relationship-between-health-related-quality-of-life-and-survival-in-metastatic-colorectal-cancer-patients-treated-with-korean-medicine
#11
Sora Park, Wankyu Eo, Sookyung Lee
OBJECTIVES: This study aimed to identify the relationship between health-related quality of life (HRQoL) measured by the Functional Assessment Cancer Therapy-General (FACT-G) and survival in metastatic colorectal cancer (mCRC) patients. METHODS: The clinical characteristics and FACT-G scores were retrospectively reviewed in mCRC patients who visited the Cancer Center of Korean Medicine. The overall survival (OS) was calculated and compared using the Kaplan-Meier method and log-rank test...
December 1, 2016: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28010185/methodological-biological-and-clinical-aspects-of-circulating-free-dna-in-metastatic-colorectal-cancer
#12
REVIEW
Karen-Lise G Spindler
BACKGROUND: Circulating DNA can be used to measure the total cell-free DNA (cfDNA) and for detection and quantification of tumor-specific genetic alterations in the peripheral blood, and the broad clinical potential of circulating DNA has attracted increasing focus over the past decade. Concentrations of circulating DNA are high in metastatic colorectal cancer (CRC), and the total levels of cfDNA have been reported to hold strong prognostic value. Colorectal tumors are characterized by a high frequency of well known, clinically relevant genetic alteration, which is readily detected in the cfDNA and holds potential for tailoring of palliative therapy and for monitoring during treatment...
January 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28008271/early-detection-of-poor-outcome-in-patients-with-metastatic-colorectal-cancer-tumor-kinetics-evaluated-by-circulating-tumor-cells
#13
Virgílio Souza E Silva, Ludmilla Thomé Domingos Chinen, Emne A Abdallah, Aline Damascena, Jociana Paludo, Rubens Chojniak, Aldo Lourenço Abbade Dettino, Celso Abdon Lopes de Mello, Vanessa S Alves, Marcello F Fanelli
BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer worldwide. New prognostic markers are needed to identify patients with poorer prognosis, and circulating tumor cells (CTCs) seem to be promising to accomplish this. PATIENTS AND METHODS: A prospective study was conducted by blood collection from patients with metastatic CRC (mCRC), three times, every 2 months in conjunction with image examinations for evaluation of therapeutic response. CTC isolation and counting were performed by Isolation by Size of Epithelial Tumor Cells (ISET)...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28007025/study-protocol-of-the-asian-xeliri-project-axept-a-multinational-randomized-non-inferiority-phase-iii-trial-of-second-line-chemotherapy-for-metastatic-colorectal-cancer-comparing-the-efficacy-and-safety-of-xeliri-with-or-without-bevacizumab-versus-folfiri-with
#14
Masahito Kotaka, Ruihua Xu, Kei Muro, Young Suk Park, Satoshi Morita, Satoru Iwasa, Hiroyuki Uetake, Tomohiro Nishina, Hiroaki Nozawa, Hiroshi Matsumoto, Kentaro Yamazaki, Sae-Won Han, Wei Wang, Joong Bae Ahn, Yanhong Deng, Sang-Hee Cho, Yi Ba, Keun-Wook Lee, Tao Zhang, Taroh Satoh, Marc E Buyse, Baek-Yeol Ryoo, Lin Shen, Junichi Sakamoto, Tae Won Kim
BACKGROUND: Capecitabine and irinotecan combination therapy (XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer (mCRC). Recently, in the Association of Medical Oncology of the German Cancer Society (AIO) 0604 trial, tri-weekly XELIRI plus bevacizumab, with reduced doses of irinotecan (200 mg/m(2) on day 1) and capecitabine (1600 mg/m(2) on days 1-14), repeated every 3 weeks, has shown favorable tolerability and efficacy which were comparable to those of capecitabine and oxaliplatin (XELOX) plus bevacizumab...
December 22, 2016: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28005260/high-early-growth-response-1-egr1-expression-correlates-with-resistance-to-anti-egfr-treatment-in-vitro-and-with-poorer-outcome-in-metastatic-colorectal-cancer-patients-treated-with-cetuximab
#15
S S Kumar, Y Tomita, J Wrin, M Bruhn, A Swalling, M Mohammed, T J Price, J E Hardingham
PURPOSE: Biomarkers, such as mutant RAS, predict resistance to anti-EGFR therapy in only a proportion of patients, and hence, other predictive biomarkers are needed. The aims were to identify candidate genes upregulated in colorectal cancer cell lines resistant to anti-EGFR monoclonal antibody treatment, to knockdown (KD) these genes in the resistant cell lines to determine if sensitivity to anti-EGFR antibody was restored, and finally to perform a pilot correlative study of EGR1 expression and outcomes in a cohort of metastatic colorectal cancer (mCRC) patients given cetuximab therapy...
December 22, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28002810/mechanisms-of-resistance-to-anti-egfr-therapy-in-colorectal-cancer
#16
REVIEW
Ben Zhao, Lu Wang, Hong Qiu, Mingsheng Zhang, Li Sun, Ping Peng, Qianqian Yu, Xianglin Yuan
Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy is effective for patients with RAS wild type metastatic colorectal cancer (mCRC). However, only a small percentage of mCRC patients are sensitive to anti-EGFR therapy and even the best cases finally become refractory to this therapy. It has become apparent that the RAS mutations correlate with resistance to anti-EGFR therapy. However, these resistance mechanisms only account for nearly 35% to 50% of nonresponsive patients, suggesting that there might be additional mechanisms...
December 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/28002313/chemotherapy-plus-bevacizumab-versus-chemotherapy-plus-cetuximab-as-first-line-treatment-for-patients-with-metastatic-colorectal-cancer-results-of-a-registry-based-cohort-analysis
#17
Long Bai, Feng Wang, Zhe-Zhen Li, Chao Ren, Dong-Sheng Zhang, Qi Zhao, Yun-Xin Lu, De-Shen Wang, Huai-Qiang Ju, Miao-Zhen Qiu, Zhi-Qiang Wang, Feng-Hua Wang, Rui-Hua Xu
The present observational cohort study was designed to elucidate the efficacy and safety profile of bevacizumab or cetuximab with chemotherapy as the first-line treatment in Chinese patients with metastatic colorectal cancer (mCRC). Clinical data were collected from a single-center registry study where mCRC patients received first-line fluoropyrimidine-based chemotherapy combined with either bevacizumab (188 patients with KRAS wild-type or mutated tumors) or cetuximab (101 patients with KRAS wild-type tumors) between January 2009 and December 2013...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28000147/erratum-to-aflibercept-a-new-way-to-target-angiogenesis-in-the-second-line-treatment-of-metastatic-colorectal-cancer-mcrc
#18
Mario Scartozzi, Loic Vincent, Marielle Chiron, Stefano Cascinu
No abstract text is available yet for this article.
December 20, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27998965/does-severe-toxicity-affect-global-quality-of-life-in-patients-with-metastatic-colorectal-cancer-during-palliative-systemic-treatment-a-systematic-review
#19
REVIEW
C S E W Schuurhuizen, A M J Braamse, I R H M Konings, M A G Sprangers, J C F Ket, J Dekker, H M W Verheul
BACKGROUND: New palliative systemic treatment regimens in patients with metastatic colorectal cancer (mCRC) have significantly improved overall survival and prognosis. These treatment regimens are often accompanied by increased toxicity, which may impair patients' quality of life (QOL). We systematically reviewed whether severe toxicity affects global QOL in patients with mCRC receiving palliative systemic treatment in recent published randomized controlled trials (RCTs). MATERIALS AND METHODS: Phase III RCTs evaluating palliative systemic treatments in patients with mCRC and published between 2004 and 2016 were considered...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27997874/digital-pcr-assessment-of-mgmt-promoter-methylation-coupled-with-reduced-protein-expression-optimises-prediction-of-response-to-alkylating-agents-in%C3%A2-metastatic-colorectal-cancer-patients
#20
Andrea Sartore-Bianchi, Filippo Pietrantonio, Alessio Amatu, Massimo Milione, Andrea Cassingena, Silvia Ghezzi, Marta Caporale, Rosa Berenato, Chiara Falcomatà, Alessio Pellegrinelli, Alberto Bardelli, Michele Nichelatti, Federica Tosi, Filippo De Braud, Federica Di Nicolantonio, Ludovic Barault, Salvatore Siena
BACKGROUND: O(6)-methylguanine-DNA-methyltransferase (MGMT) is a repair protein, and its deficiency makes tumours more susceptible to the cytotoxic effect of alkylating agents. Five clinical trials with temozolomide or dacarbazine have been performed in metastatic colorectal cancer (mCRC) with selection based on methyl-specific PCR (MSP) testing with modest results. We hypothesised that mitigated results are consequences of unspecific patient selection and that alternative methodologies for MGMT testing such as immunohistochemistry (IHC) and digital polymerase chain reaction (PCR) could enhance patient enrolment...
January 2017: European Journal of Cancer
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