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https://www.readbyqxmd.com/read/27907852/the-relevance-of-primary-tumour-location-in-patients-with-metastatic-colorectal-cancer-a-meta-analysis-of-first-line-clinical-trials
#1
Julian Walter Holch, Ingrid Ricard, Sebastian Stintzing, Dominik Paul Modest, Volker Heinemann
BACKGROUND: Retrospective subgroup analyses suggest that primary tumour location (PTL) has a prognostic importance and relates to response to targeted therapy. METHODS: We conducted a meta-analysis of first-line clinical trials available up to October 2016, which assessed the relevance of PTL in patients with metastatic colorectal cancer (mCRC). Right- and left-sided colorectal cancers were differentiated (RC and LC). RESULTS: In 13 first-line randomised controlled trials and one prospective pharmacogenetic study, RC was associated with a significantly worse prognosis compared with LC (hazard ratio [HR] for overall survival: 1...
November 28, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27899972/efficacy-and-safety-of-aflibercept-in-metastatic-colorectal-cancer-pretreated-with-bevacizumab-a-report-of-five-cases
#2
Julia Alcaide, Mayte Delgado, Marta Legerén, José Miguel Jurado, Isabel Blancas, Teresa Pereda, Jorge López, Margarita Garrido, María J Sánchez, José L García, Antonio Rueda
Aflibercept is a recombinant fusion protein that acts by inhibiting tumoural angiogenesis. Efficacy data obtained in the VELOUR randomised study has contributed to the approval of aflibercept as a second-line metastatic colorectal cancer (mCRC) treatment following an oxaliplatin-based regimen. The present study reports a case series of five patients with mCRC, who were treated in two centres since 2011 in the Compassionate Use Program for aflibercept. All patients had a KRAS mutation and previously received palliative fluoropyrimidine-oxaliplatin-based chemotherapy with bevacizumab...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899088/alternative-splicing-of-estrogen-receptor-alpha-in-hepatocellular-carcinoma
#3
Jian Zhang, Jianwei Ren, Jiamin Wei, Charing C N Chong, Dongjie Yang, Yulong He, George G Chen, Paul B S Lai
BACKGROUND: The role of estrogen receptor alpha (ERa), estrogen receptor beta (ERb) and ERa36 signaling in hepatocellular carcinoma (HCC) is not fully addressed. METHODS: In this study, three cohorts were included: (i) primary HCC patients (N = 76, cohort P), (ii) colorectal liver metastasis (mCRC) (N = 32, cohort S), and (iii) HCC from The Cancer Genome Atlas (TCGA) (N = 121). The levels of ERa36 and wtER36 were measured and their correlation with clinicopathologic features was determined...
November 30, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27891617/signet-ring-cell-carcinoma-of-resectable-metastatic-colorectal-cancer-has-rare-surgical-value
#4
Jianfei Fu, Lunpo Wu, Mengjie Jiang, Yinuo Tan, Dan Li, Fei Chen, Ting Jiang, Jinlin Du
BACKGROUND AND OBJECTIVES: Signet ring cell carcinoma (SRCC) is a uniquely separated subgroup in metastatic colorectal cancer (mCRC). The aims are to investigate the value of resection in patients with resectable metastatic signet ring cell colorectal cancer. METHODS: Patients with mCRC who underwent resection in Surveillance, Epidemiology, and End Results database during 1998-2010 were retrospectively analyzed. Kaplan-Meier and COX models were used to analyze the differences in the survival...
November 27, 2016: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27889786/targeted-therapy-of-colorectal-cancer
#5
Andreas Seeber, Günther Gastl
Over the past decades, considerable progress has been made in the management of colorectal cancer (CRC), leading to a significant improvement in overall survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of CRC and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article, we will discuss various targeted therapies in the management of metastatic CRC (mCRC)...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27888624/rhoa-regulates-resistance-to-irinotecan-by-regulating-membrane-transporter-and-apoptosis-signaling-in-colorectal-cancer
#6
Huang Ruihua, Zhang Mengyi, Zhao Chong, Qiu Meng, Ma Xin, Tang Qiulin, Bi Feng, Liu Ming
Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. While surgery remains the mainstay of treatment in early stage CRC, chemotherapy is usually given to prolong the overall survival and improve the quality of life for metastatic colorectal cancer (mCRC). But drug resistance is one of the major hurdles of mCRC treatment, and the underlying mechanisms are still largely unknown. In this study, we show that, compared with parental cells, RhoA is up-regulated in irinotecan (CPT-11)-resistant CRC cells...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888621/intraperitoneal-ziv-aflibercept-effectively-manages-refractory-ascites-in-colorectal-cancer-patients
#7
Chieh-Sheng Lu, Jen-Kou Lin, Wei-Shone Chen, Tzu-Chen Lin, Jeng-Kai Jiang, Shung-Haur Yang, Huann-Sheng Wang, Shih-Ching Chang, Yuan-Tzu Lan, Chun-Chi Lin, Hung-Hsin Lin, Hao-Wei Teng
Ascites related to metastatic colorectal cancer (mCRC) reduces patient survival and quality of life, and systemic chemotherapy is largely ineffective for managing ascites. Here, we examined the clinical efficacy of intraperitoneal (IP) ziv-aflibercept for managing refractory ascites in 15 mCRC patients who did not respond to standard chemotherapy. Fifty or 100 mg of ziv-aflibercept in 100 mL of saline solution were infused through a pigtail catheter and retained for 24 h. When the ascites drainage volumes were subsequently monitored, 73...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888325/total-lesion-glycolysis-tlg-as-an-imaging-biomarker-in-metastatic-colorectal-cancer-patients-treated-with-regorafenib
#8
Yoojoo Lim, Ji-In Bang, Sae-Won Han, Jin Chul Paeng, Kyung-Hun Lee, Jee Hyun Kim, Gyeong Hoon Kang, Seung-Yong Jeong, Kyu Joo Park, Tae-You Kim
PURPOSE: This study was performed to evaluate whether fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) could predict treatment outcome of regorafenib in metastatic colorectal cancer (mCRC). METHODS: Previously treated refractory mCRC patients were enrolled into a prospective biomarker study of regorafenib. For this sub-study, the results of FDG PET/CT scans at baseline and after two cycles of treatment were analyzed. Various metabolic parameters obtained from PET images were analyzed in relation to treatment outcome...
November 25, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27885818/the-impact-of-bevacizumab-in-metastatic-colorectal-cancer-with-an-intact-primary-tumor-results-from-a-large-prospective-cohort-study
#9
Belinda Lee, Hui-Li Wong, Mark Tacey, Jeanne Tie, Rachel Wong, Margaret Lee, Louise Nott, Jeremy Shapiro, Ross Jennens, Natalie Turner, Ben Tran, Sumitra Ananda, Desmond Yip, Gary Richardson, Phillip Parente, Lionel Lim, Greg Stefanou, Matthew Burge, Mahesh Iddawela, Jeremy Power, Peter Gibbs
BACKGROUND: Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood. METHODS: Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT...
November 25, 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27878357/on-treatment-markers-as-predictors-to-guide-anti-egfr-moab-treatment-in-metastatic-colorectal-cancer-a-systematic-review-with-meta-analysis
#10
REVIEW
Jing Hu, Zhen Zhang, Rui Zheng, Lei Cheng, Mi Yang, Li Li, Baorui Liu, Xiaoping Qian
PURPOSE: Skin toxicity (ST) and early tumor shrinkage (ETS) are early phenomenon during the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) treatment. We conducted a meta-analysis and included relevant studies that reported the impact of ST and ETS on survival- and life quality-based outcome of metastatic colorectal cancer (mCRC) patients treated with anti-EGFR MoAb. METHODS: Relevant studies were identified from PubMed and Embase reporting the correlation of ST and ETS with the clinical outcome of mCRC patients treated with anti-EGFR MoAb...
November 22, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27878354/randomized-phase-ii-study-of-cetuximab-versus-irinotecan-and-cetuximab-in-patients-with-chemo-refractory-kras-codon-g13d-metastatic-colorectal-cancer-g13d-study
#11
Masato Nakamura, Toru Aoyama, Keiichiro Ishibashi, Akihito Tsuji, Yasutaka Takinishi, Yoshiaki Shindo, Junichi Sakamoto, Koji Oba, Hideyuki Mishima
PURPOSE: This study investigated the efficacy and safety of cetuximab-based treatment in patients with chemotherapy-resistant refractory mCRC with KRAS G13D mutation. PATIENTS AND METHODS: An assessment of the efficacy and safety of cetuximab-based treatment was performed in an observation-enriched randomized controlled study comparing the cetuximab alone group (Cet group) and the combination of cetuximab and irinotecan group (CetI group) for KRAS G13D-mutated mCRC in Japan...
November 22, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27866244/efficacy-and-safety-of-nab-paclitaxel-in-patients-with-previously-treated-metastatic-colorectal-cancer-a-phase-ii-colo-001-trial
#12
Michel Ducreux, Jaafar Bennouna, Antoine Adenis, Thierry Conroy, Astrid Lièvre, Fabienne Portales, Julie Jeanes, Li Li, Alfredo Romano
PURPOSE: This single-arm, phase II trial evaluated nab-paclitaxel monotherapy in pretreated patients with metastatic colorectal cancer (mCRC). METHODS: Patients with mCRC (RAS wild-type and RAS mutant cohorts) received nab-paclitaxel 125 mg/m(2) days 1, 8, and 15 (28-day cycle). The primary endpoint was investigator-assessed progression-free survival (PFS) rate at week 8; secondary endpoints included overall survival, overall response rate, and safety. Stage 1 planned enrollment was 15 patients per cohort per Simon 2-stage design...
November 19, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27866194/efficacy-of-bevacizumab-in-the-first-line-treatment-of-patients-with-ras-mutations-metastatic-colorectal-cancer-a-systematic-review-and-network-meta-analysis
#13
Mingyi Zhou, Ping Yu, Jinglei Qu, Ying Chen, Yang Zhou, Lingyu Fu, Jingdong Zhang
BACKGROUND/AIMS: Whether patients with RAS mutation metastatic colorectal cancer (mCRC) obtain benefits from bevacizumab added to first-line chemotherapy remains unclear. METHODS: PubMed, Cochrane Systematic Reviews, the Cochrane Collaboration Central Register of Controlled Clinical Trials, ClinicalTrials.gov, and the American Society of Clinical Oncology and European Society for Medical Oncology databases were searched to identify abstracts for randomized controlled trials (RCTs) evaluating the efficacy of bevacizumab for the first-line treatment of patients with RAS mutations mCRC from inception to the end of April 2016...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27865140/overcoming-dynamic-molecular-heterogeneity-in-metastatic-colorectal-cancer-multikinase-inhibition-with-regorafenib-and-the-case-of-rechallenge-with-anti-egfr
#14
REVIEW
Andrea Sartore-Bianchi, Salvatore Siena, Giuseppe Tonini, Alberto Bardelli, Daniele Santini
In metastatic colorectal cancer (mCRC), fluorouracil-based combination therapy with oxaliplatin or irinotecan is the mainstay of first-line treatment. Patient survival has been significantly improved with the introduction of monoclonal antibodies against VEGF (bevacizumab), VEGFR2 (ramucirumab) or EGFR (cetuximab or panitumumab) in first- and second-line therapies. However, all patients treated with chemotherapy and targeted therapies will eventually relapse, and recently the emergence of alterations in EGFR, RAS, BRAF, ERB-B2, MET and possibly in other genes has been shown to jeopardize response to EGFR blockade...
October 29, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27864220/estimating-12-weeks-death-probability-in-patients-with-refractory-metastatic-colorectal-cancer-the-colon-life-nomogram
#15
F Pietrantonio, R Miceli, L Rimassa, S Lonardi, G Aprile, A Mennitto, F Marmorino, S Bozzarelli, L Antonuzzo, E Tamburini, F Morano, D Rossini, F Battaglin, M Baretti, R Berenato, V Formica, S Mosconi, F Petrelli, M Ghidini, F Loupakis, D Spada, S Cinieri, G Beretta, A Falcone, F de Braud, C Cremolini
BACKGROUND: Regorafenib and TAS-102 have recently demonstrated statistically significant survival gains in patients with refractory metastatic colorectal cancer (mCRC). Life expectancy ≥12 weeks was an inclusion criterion in registrative trials, and the identification of proper clinical selection tools for the daily use of these drugs in heavily pre-treated patients is needed to improve the cost-benefit ratio. We aimed at building a nomogram able to predict death probability within 12 weeks from the date of assessment of refractory mCRC...
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27864115/synergistic-antitumor-activity-of-regorafenib-and-lapatinib-in-preclinical-models-of-human-colorectal-cancer
#16
Wen-Ji Zhang, Yong Li, Meng-Ning Wei, Yao Chen, Jian-Ge Qiu, Qi-Wei Jiang, Yang Yang, Di-Wei Zheng, Wu-Ming Qin, Jia-Rong Huang, Kun Wang, Wen-Juan Zhang, Yi-Jun Wang, Dong-Hua Yang, Zhe-Sheng Chen, Zhi Shi
Regorafenib significantly prolongs overall survival in patients with metastatic colorectal cancer (mCRC), but the overall clinical efficacy of regorafenib remains quite limited. Combination chemotherapy is a potentially promising approach to enhance anticancer activity, overcome drug resistance, and improve disease-free and overall survival. The current study investigates the antitumor activity of regorafenib in combination with lapatinib in preclinical models of human CRC. Our results show improved antitumor efficacy when regorafenib is combined with lapatinib both in vitro and in vivo...
November 15, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27861344/efficacy-and-safety-of-addition-of-bevacizumab-to-folfiri-or-irinotecan-bolus-5-fu-lv-ifl-in-patients-with-metastatic-colorectal-cancer-a-meta-analysis
#17
Ke Chen, Yinya Gong, Qi Zhang, Yanping Shen, Taoqi Zhou
Recent studies have paid much attention on the safety of bevacizumab as adjuvant chemotherapy for metastatic colorectal cancer. The aim of this meta-analysis was to study the efficacy and safety of bevacizumab in combination with irinotecan, bolus followed by infusional 5-fluorouracil, and leucovorin (FOLFIRI) and, irinotecan, bolus fluorouracil, leucovorin (IFL) for patients with metastatic colorectal cancer (mCRC).An electronic search of related trials was conducted from PubMed, EMBASE, Cochrane Library databases...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27857020/surrogate-endpoints-in-second-line-trials-of-targeted-agents-in-metastatic-colorectal-cancer-a-literature-based-systematic-review-and-meta-analysis
#18
Chiara Cremolini, Carlotta Antoniotti, Filippo Pietrantonio, Rosa Berenato, Marco Tampellini, Chiara Baratelli, Lisa Salvatore, Federica Marmorino, Beatrice Borelli, Federico Nichetti, Paolo Bironzo, Cristina Sonetto, Maria Di Bartolomeo, Filippo de Braud, Fotios Loupakis, Alfredo Falcone, Massimo Di Maio
Purpose: To evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC). Materials and Methods: A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R2)...
November 15, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27856123/prognostic-impact-of-primary-tumor-location-on-clinical-outcomes-of-metastatic-colorectal-cancer-treated-with-cetuximab-plus-oxaliplatin-based-chemotherapy-a-subgroup-analysis-of-the-jaccro-cc-05-06-trials
#19
Yu Sunakawa, Wataru Ichikawa, Akihito Tsuji, Tadamichi Denda, Yoshihiko Segawa, Yuji Negoro, Ken Shimada, Mitsugu Kochi, Masato Nakamura, Masahito Kotaka, Hiroaki Tanioka, Akinori Takagane, Satoshi Tani, Tatsuro Yamaguchi, Takanori Watanabe, Masahiro Takeuchi, Masashi Fujii, Toshifusa Nakajima
INTRODUCTION: Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. PATIENTS AND METHODS: The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022)...
October 6, 2016: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/27852040/clinical-validation-of-prospective-liquid-biopsy-monitoring-in-patients-with-wild-type-ras-metastatic-colorectal-cancer-treated-with-folfiri-cetuximab
#20
Rodrigo A Toledo, Antonio Cubillo, Estela Vega, Elena Garralda, Rafael Alvarez, Lisardo U de la Varga, Jesús R Pascual, Gema Sánchez, Francesca Sarno, Susana H Prieto, Sofía Perea, Pedro P Lopéz-Casas, Fernando López-Ríos, Manuel Hidalgo
Cancer genomics and translational medicine rely on the molecular profiling of patient's tumor obtained during surgery or biopsy. Alternatively, blood is a less invasive source of tumor DNA shed, amongst other ways, as cell-free DNA (cfDNA). Highly-sensitive assays capable to detect cancer genetic events from patient's blood plasma became popularly known as liquid biopsy (LqB). Importantly, retrospective studies including small number of selected patients with metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapy have shown LqB capable to detect the acquired clonal mutations in RAS genes leading to therapy resistance...
November 11, 2016: Oncotarget
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