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https://www.readbyqxmd.com/read/28633089/first-line-panitumumab-plus-folfox4-or-folfiri-in-colorectal-cancer-with-multiple-or-unresectable-liver-metastases-a-randomised-phase-ii-trial-planet-ttd
#1
Alfredo Carrato, Albert Abad, Bartomeu Massuti, Cristina Grávalos, Pilar Escudero, Federico Longo-Muñoz, José-Luis Manzano, Auxiliadora Gómez, María José Safont, Javier Gallego, Beatriz García-Paredes, Carles Pericay, Rosario Dueñas, Fernando Rivera, Ferrán Losa, Manuel Valladares-Ayerbes, Encarnación González, Enrique Aranda
BACKGROUND: In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. METHODS: Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI...
June 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28626084/optimization-of-ras-braf-mutational-analysis-confirms-improvement-in-patient-selection-for-clinical-benefit-to-anti-egfr-treatment-in-metastatic-colorectal-cancer
#2
Cristina Santos, Daniel Azuara, Rocio Garcia-Carbonero, Pilar García Alfonso, Alfredo Carrato, Elena Elez, Auxiliadora Gómez, Ferran Losa, Clara Montagut, Bartomeu Massuti, Valenti Navarro, Mar Varela, Adriana López-Doriga, Victor Moreno, Manuel Valladares, Jose Luis Manzano, José Maria Viéitez, Enrique Aranda, Xavier Sanjuan, Josep Tabernero, Gabriel Capella, Ramon Salazar
In metastatic colorectal cancer (mCRC) recent studies have shown the importance to accurately quantify low-abundance mutations of RAS pathway because anti-EGFR therapy may depend on certain mutation thresholds. We aimed to evaluate the added predictive value of extended RAS panel testing using two commercial assays and a highly sensitive and quantitative digital PCR (dPCR). Tumor samples from 583 mCRC patients treated with anti-EGFR (n=255) or bevacizumab (n=328) based therapies from several clinical trials and retrospective series from the TTD/RTICC Spanish network were analyzed by cobas®, therascreen® and dPCR...
June 16, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28622036/molecular-targeted-drugs-and-treatment-of-colorectal-cancer-recent-progress-and-future-perspectives
#3
Fang Geng, Zheng Wang, Hang Yin, Junxian Yu, Bangwei Cao
Nowadays, colorectal cancer is the fourth most common type of tumor all over the world. When diagnosed, ∼50%-60% of tumors have metastasized, thus resulting in a grim prognosis. Chemotherapy is regarded as standard treatment for patients with colorectal cancer, however, limitations of chemotherapy cannot be ignored, such as low selectivity, insufficient concentrations in tumor tissues, and systemic toxicity. Recently, six targeted drugs have been approved by the U.S. Food and Drug Administration (FDA) for treatment of metastatic colorectal cancer (mCRC), including bevacizumab, aflibercept, regorafenib, cetuximab, and panitumumab...
June 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28619608/real-world-direct-health-care-costs-for-metastatic-colorectal-cancer-patients-treated-with-cetuximab-or-bevacizumab-containing-regimens-in-first-line-or-first-line-through-second-line-therapy
#4
Stephen Johnston, Kathleen Wilson, Helen Varker, Elisabetta Malangone-Monaco, Paul Juneau, Ellen Riehle, Sacha Satram-Hoang, Nicolas Sommer, Sarika Ogale
BACKGROUND: The present study examined real-world direct health care costs for metastatic colorectal cancer (mCRC) patients initiating first-line (1L) bevacizumab (BEV)- or cetuximab (CET)-containing regimen in 1L or 1L-through-second-line (1L-2L) therapy. PATIENTS AND METHODS: Using a large US insurance claims database, patients with mCRC initiating 1L BEV- or 1L CET-containing regimen from January 1, 2008 to September 30, 2014 were identified. The per-patient per-month (PPPM) all-cause health care costs (2014 US dollars) were measured during 1L therapy and, for patients continuing to a 2L biologic-containing regimen, 1L-2L therapy...
March 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28618430/extreme-assay-sensitivity-in-molecular-diagnostics-further-unveils-intratumour-heterogeneity-in-metastatic-colorectal-cancer-as-well-as-artifactual-low-frequency-mutations-in-the-kras-gene
#5
Sara Mariani, Luca Bertero, Simona Osella-Abate, Cristiana Di Bello, Paola Francia di Celle, Vittoria Coppola, Anna Sapino, Paola Cassoni, Caterina Marchiò
BACKGROUND: Gene mutations in the RAS family rule out metastatic colorectal carcinomas (mCRCs) from anti-EGFR therapies. METHODS: We report a retrospective analysis by Sequenom Massarray and fast COLD-PCR followed by Sanger sequencing on 240 mCRCs. RESULTS: By Sequenom, KRAS and NRAS exons 2-3-4 were mutated in 52.9% (127/240) of tumours, while BRAF codon 600 mutations reached 5% (12/240). Fast COLD-PCR found extra mutations at KRAS exon 2 in 15/166 (9%) of samples, previously diagnosed by Sequenom as wild-type or mutated at RAS (exons 3-4) or BRAF genes...
June 15, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28612618/durable-complete-response-of-colorectal-cancer-metastasis-after-biochemotherapy
#6
M Honzirkova, L Lipská, P Kohout, J Ferda, O Bělohlávek, T Büchler
BACKGROUND: Resection of the metastatic site is indicated but not always possible in patients with metastatic colorectal cancer (mCRC) who achieve a partial or complete response (CR) to induction systemic treatment. CR after systemic treatment alone is uncommon, and even patients with radiologic CR after induction chemotherapy harbour persistent macroscopic or microscopic residual disease in more than 80% of cases. Occasionally, some metastatic lesions disappear radiologically but others persist after induction systemic treatment...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28608814/predicting-outcome-and-therapy-response-in-mcrc-patients-using-an-indirect-method-for-ctcs-detection-by-a-multigene-expression-panel-a-multicentric-prospective-validation-study
#7
Yolanda Vidal Insua, Juan de la Cámara, Elena Brozos Vázquez, Ana Fernández, Francisca Vázquez Rivera, Mª José Villanueva Villanueva Silva, Jorge Barbazán, Laura Muinelo-Romay, Sonia Candamio Folgar, Alicia Abalo, Rafael López-López, Miguel Abal, Lorena Alonso-Alconada
Colorectal cancer (CRC) is one of the major causes of cancer-related deaths. Early detection of tumor relapse is crucial for determining the most appropriate therapeutic management. In clinical practice, computed tomography (CT) is routinely used, but small tumor changes are difficult to visualize, and reliable blood-based prognostic and monitoring biomarkers are urgently needed. The aim of this study was to prospectively validate a gene expression panel (composed of GAPDH, VIL1, CLU, TIMP1, TLN1, LOXL3 and ZEB2) for detecting circulating tumor cells (CTCs) as prognostic and predictive tool in blood samples from 94 metastatic CRC (mCRC) patients...
June 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28599498/sequential-administration-of-xelox-and-xeliri-is-effective-feasible-and-well-tolerated-by-patients-with-metastatic-colorectal-cancer
#8
Taro Fukui, Koichi Suzuki, Kosuke Ichida, Yuji Takayama, Nao Kakizawa, Yuta Muto, Fumi Hasegawa, Fumiaki Watanabe, Rina Kikugawa, Masaaki Saito, Shingo Tsujinaka, Yasuyuki Miyakura, Toshiki Rikiyama
Sequential administration of the chemotherapy regimes capecitabine and oxaliplatin (XELOX) and capecitabine and irinotecan (XELIRI) in the first- to second-line treatment setting would allow patients to be managed more easily in an outpatient unit. However, a small number of studies have raised concerns of cumulative adverse events as a consequence of the continuous use of capecitabine. To investigate this, the present study conducted a retrospective review of 81 consecutive metastatic colorectal cancer (mCRC) patients treated with the oxaliplatin, fluorouracil and leucovorin-irinotecan, fluorouracil and leucovorin (FOLFOX-FOFIRI/F-F) regimen (n=40) or the XELOX-XELIRI (X-X) regimen (n=41) in first- to second-line chemotherapy in Saitama Medical Center between 2006 and 2012...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28598398/right-vs-left-sided-metastatic-colorectal-cancer-differences-in-tumor-biology-and-bevacizumab-efficacy
#9
Paola Ulivi, Emanuela Scarpi, Elisa Chiadini, Giorgia Marisi, Martina Valgiusti, Laura Capelli, Andrea Casadei Gardini, Manlio Monti, Silvia Ruscelli, Giovanni Luca Frassineti, Daniele Calistri, Dino Amadori, Alessandro Passardi
There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter "Italian Trial in Advanced Colorectal Cancer (ITACa)", randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B)...
June 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28595137/health-related-quality-of-life-in-patients-with-metastatic-colorectal-cancer-association-with-systemic-inflammatory-response-and-ras-and-braf-mutation-status
#10
Maria Thomsen, Marianne Grønlie Guren, Eva Skovlund, Bengt Glimelius, Marianne Jensen Hjermstad, Julia S Johansen, Elin Kure, Halfdan Sorbye, Per Pfeiffer, Thoralf Christoffersen, Tormod Kyrre Guren, Kjell Magne Tveit
BACKGROUND: The aim of this study was to evaluate the effect of cetuximab on health-related quality of life (HRQoL) in the NORDIC-VII trial on metastatic colorectal cancer (mCRC), and to assess HRQoL in relation to RAS and BRAF mutation status and inflammatory biomarkers. PATIENT AND METHODS: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, after every fourth cycle of chemotherapy, and at the end of treatment...
June 5, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28592621/bevacizumab-for-metastatic-colorectal-cancer-a-global-cost-effectiveness-analysis
#11
Daniel A Goldstein, Qiushi Chen, Turgay Ayer, Kelvin K W Chan, Kiran Virik, Ariel Hammerman, Baruch Brenner, Christopher R Flowers, Peter S Hall
BACKGROUND: In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel. METHODS: We performed the analysis using a previously established Markov model for mCRC...
June 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28588777/the-combination-of-systemic-chemotherapy-and-local-treatment-may-improve-the-survival-of-patients-with-unresectable-metastatic-colorectal-cancer
#12
Jiemin Zhao, Liangrong Shi, Mei Ji, Jun Wu, Changping Wu
With the development of systemic chemotherapy, the survival time of patients with advanced colorectal cancer (CRC) has increased. In addition, local treatments, such as microwave ablation and radioactive seed implantation, have been shown to be effective. However, the number of studies reporting on the effect of systemic chemotherapy combined with local treatments is limited. The present study was conducted to determine the effect of local treatment combined with systemic chemotherapy in patients with initial unresectable metastatic CRC (mCRC)...
June 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28582279/prevalence-and-influence-on-outcome-of-her2-neu-her3-and-nrg1-expression-in-patients-with-metastatic-colorectal-cancer
#13
Arndt Stahler, Volker Heinemann, Jens Neumann, Alexander Crispin, Andreas Schalhorn, Sebastian Stintzing, Clemens Giessen-Jung, Ludwig Fischer von Weikersthal, Ursula Vehling-Kaiser, Martina Stauch, Detlef Quietzsch, Julian W Holch, Stephan Kruger, Michael Haas, Marlies Michl, Jobst von Einem, Thomas Kirchner, Andreas Jung, Dominik P Modest
Our aim was to explore the impact of the HER2/neu, HER3 receptor as well as their ligands' neuregulin (NRG1) expression on the outcome of patients with metastatic colorectal cancer (mCRC). NRG1, HER2/neu and HER3 expression was evaluated in 208 patients with mCRC receiving 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as the first-line treatment. Biomarker expression was correlated with the outcome of patients. NRG1 (low: 192 vs. high: 16), HER2/neu (low: 201 vs. high: 7) and HER3 (low: 69 vs. high: 139) expressions were assessed in 208 patients...
June 2, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28580363/targeted-metabolomics-in-colorectal-cancer-a-strategic-approach-using-standardized-laboratory-tests-of-the-blood-and-urine
#14
Katarzyna J Jerzak, Marissa Laureano, Radwa Elsharawi, Peter Kavsak, Kelvin Kw Chan, Sukhbinder K Dhesy-Thind, Kevin Zbuk
BACKGROUND: Glycolytic markers have been detected in colorectal cancer (CRC) using advanced analytical methods. METHODS: Using commercially available assays, by-products of anaerobic metabolism were prospectively measured in the blood and urine of 20 patients with metastatic colorectal cancer (mCRC) and 20 patients with local disease. Twenty-four-hour urine citrate, plasma lactate, ketones, venous blood gas, anion gap, and osmolar gap were investigated. Results of patients with metastatic and local CRC were compared using two-sample t-tests or equivalent nonparametric tests...
2017: Hypoxia
https://www.readbyqxmd.com/read/28576867/early-evaluation-of-circulating-tumor-dna-as-marker-of-therapeutic-efficacy-in-metastatic-colorectal-cancer-patients-placol-study
#15
Fanny Garlan, Pierre Laurent-Puig, David Sefrioui, Nathalie Siauve, Audrey Didelot, Nasrin Sarafan-Vasseur, Pierre Michel, Geraldine Perkins, Claire Mulot, Hélène Blons, Julien Taieb, Frederic Di Fiore, Valerie Taly, Aziz Zaanan
Purpose. Markers of chemotherapy efficacy in metastatic colorectal cancer (mCRC) are essential for optimization of treatment strategies. We evaluated the applicability of early changes in circulating tumor DNA (ctDNA) as a marker of therapeutic efficacy. <p>Experimental design. This prospective study enrolled consecutive mCRC patients receiving a first- or second-line chemotherapy. CtDNA was assessed in plasma collected before the first (C0), second (C1) and/or third (C2) chemotherapy cycle, using picodroplet-digital PCR assays based either on detection of gene mutation (KRAS, BRAF, TP53) or hypermethylation (WIF1, NPY)...
June 2, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28576857/braf-mutations-as-predictive-biomarker-for-response-to-anti-egfr-monoclonal-antibodies
#16
Emilie M J van Brummelen, Anthonius de Boer, Jos H Beijnen, Jan H M Schellens
Recently, the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) recommended that patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer could be treated with anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab only in absence of Rat-Sarcoma (RAS) mutations. In addition to the previously established biomarker Kirsten rat sarcoma viral oncogene homolog (KRAS) exon 2, cumulative evidence also shows that patients whose tumors harbor KRAS exons 3 or 4 and neuroblastoma rat-sarcoma viral oncogene homolog (NRAS) exons 2, 3, and 4 mutations are found unlikely to benefit from anti-EGFR treatment...
June 2, 2017: Oncologist
https://www.readbyqxmd.com/read/28576381/agreement-between-hospital-discharge-diagnosis-codes-and-medical-records-to-identify-metastatic-colorectal-cancer-and-associated-comorbidities-in-elderly-patients
#17
A Gouverneur, D Dolatkhani, M Rouyer, A Grelaud, F Francis, V Gilleron, A Fourrier-Réglat, P Noize
BACKGROUND: Quality of coding to identify cancers and comorbidities through the French hospital diagnosis database (Programme de médicalisation des systèmes d'information, PMSI) has been little investigated. Agreement between medical records and PMSI database was evaluated regarding metastatic colorectal cancer (mCRC) and comorbidities. METHODS: From 01/01/2013 to 06/30/2014, 74 patients aged≥65years at mCRC diagnosis were identified in Bordeaux teaching hospital...
May 30, 2017: Revue D'épidémiologie et de Santé Publique
https://www.readbyqxmd.com/read/28571114/population-modelling-integrating-pharmacokinetics-pharmacodynamics-pharmacogenetics-and-clinical-outcome-in-sunitinib-treated-cancer-patients
#18
M H Diekstra, A Fritsch, F Kanefendt, J J Swen, Djar Moes, F Sörgel, M Kinzig, C Stelzer, D Schindele, T Gauler, S Hauser, D Houtsma, M Roessler, B Moritz, K Mross, L Bergmann, E Oosterwijk, L A Kiemeney, H J Guchelaar, U Jaehde
The tyrosine kinase inhibitor sunitinib is used as first-line therapy in patients with metastasized renal cell carcinoma (mRCC), given in fixed-dose regimens despite its high variability in pharmacokinetics. Inter-individual variability of drug exposure may be responsible for differences in response. Therefore, dosing strategies based on pharmacokinetic and pharmacodynamic (PK/PD) models may be useful to optimize treatment. Plasma concentrations of sunitinib, its active metabolite SU12662 and the soluble VEGF receptors sVEGFR-2 and sVEGFR-3 were measured in 26 mRCC patients within the EuroTARGET project and 21 metastasized colorectal cancer (mCRC) patients from the C-II-005 study...
June 1, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28569041/predictive-value-of-tlr7-polymorphism-for-cetuximab-based-chemotherapy-in-patients-with-metastatic-colorectal-cancer
#19
Satoshi Okazaki, Sebastian Stintzing, Yu Sunakawa, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Satoshi Matsusaka, Martin D Berger, Yuji Miyamoto, Mitsukuni Suenaga, Marta Schirripa, Jordan D West, Roel Gopez, Tsuji Akihito, Wataru Ichikawa, Volker Heinemann, R William DePaolo, Heinz-Josef Lenz
The TLR7 and TLR9 signalings are implicated in the regulation of the immune system through type-I interferon induction. Preclinical studies have demonstrated the immunomodulatory and antitumor effects of TLR7 and TLR9 agonists in combination with cetuximab. We tested the hypothesis that genetic variations in TLR7 and TLR9 and their downstream molecules IRF5 and IRF7 were associated with outcomes in metastatic colorectal cancer (mCRC) patients receiving cetuximab-based chemotherapy. Six single nucleotide polymorphisms (SNPs) in TLR7, TLR9, IRF5 and IRF7 were tested for the association with RR, PFS, and OS in KRAS-wild type mCRC patients...
May 31, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28561718/systemic-therapy-for-metastatic-colorectal-cancer-from-current-standards-to-future-molecular-targeted-approaches
#20
Chloe E Atreya, Rona Yaeger, Edward Chu
Over the past 20 years, substantial advances have been made in the treatment of patients with metastatic colorectal cancer (mCRC). In particular, there is now a wide range of options for the front-line treatment of mCRC. Sophisticated molecular technologies have been developed to identify novel prognostic and predictive biomarkers for CRC. DNA sequencing technology has made remarkable advances in recent years, primarily as a result of the development of next-generation sequencing and whole exome sequencing, which are powerful new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of personalized medicine...
2017: American Society of Clinical Oncology Educational Book
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