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Magali Rouyer, Eric François, Antonio Sa Cunha, Alain Monnereau, Pernelle Noize, Philip Robinson, Cécile Droz-Perroteau, Alise Le Monies de Sagazan, Jérémy Jové, Régis Lassalle, Nicholas Moore, Annie Fourrier-Réglat, Denis Smith
INTRODUCTION: Few real-life data are available on cetuximab benefit. The EREBUS cohort was performed to assess metastases resection rate, use, safety, and survival outcomes in wild-type KRAS (Kirsten rat sarcoma viral oncogene) patients with initially unresectable metastatic colorectal cancer (mCRC) treated by cetuximab in real practice. PATIENTS AND METHODS: The study cohort comprised patients initiating cetuximab between January 2009 and December 2010 in 65 French centers, with initially unresectable mCRC and wild-type KRAS...
January 31, 2018: Clinical Colorectal Cancer
Marta Schirripa, Wu Zhang, Dongyun Yang, Shu Cao, Satoshi Okazaki, Fotios Loupakis, Martin D Berger, Yan Ning, Yuji Miyamoto, Mitsukuni Suenaga, Giulia Alberti, Jordan D West, Sara Lonardi, Taline Khoukaz, Francesca Bergamo, Francesca Battaglin, Carlotta Antoniotti, Alfredo Falcone, Sebastian Stintzing, Volker Heinemann, Heinz-Josef Lenz
BACKGROUND: Macrophages play a crucial role in the interaction between tumor and immune system, and iNOS is known as a surrogate marker of M1 macrophages activation. The goal of the study was to investigate the role of iNOS polymorphisms as prognostic marker in mCRC patients. MATERIALS AND METHODS: Functional significant polymorphisms in the promoter of INOS gene were analyzed by PCR-based and direct DNA sequencing in 4 cohorts of patients receiving bevacizumab based first-line chemotherapy: two evaluation cohorts (TRIBE ARM A and ARM B) and two validation cohorts (FIRE 3 arm A and MOMA)...
2018: PloS One
Datian Chen, Li Li, Xiang Zhang, Guangyi Gao, Lili Shen, Jing Hu, Mi Yang, Baorui Liu, Xiaoping Qian
BACKGROUND: The efficacy of oxaliplatin-based chemotherapy combined with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) remains controversial in metastatic colorectal cancer (mCRC). This meta-analysis aims to estimate the effect of adding panitumumab or cetuximab to oxaliplatin-based chemotherapy in RAS wild type mCRC patients for the first-line treatment. The primary tumor location is also considered into this meta-analysis. METHODS: RCT studies were identified by a search of MEDLINE, EMBASE, Cochrane library to October 2017, supplemented by manually retrieving ASCO, ESMO conference abstracts...
March 2018: Medicine (Baltimore)
Volker Kaechele, Jürgen Hess, Wolfgang Schneider-Kappus
Trifluridine/tipiracil (FTD/TPI) significantly improves overall survival in patients with metastatic colorectal cancer (mCRC). The most common treatment-related event (grade ≥3) was hematological toxicity. We here report long-term disease-stabilizing FTD/TPI treatment of an mCRC patient (KRAS wild-type, ECOG performance status 1 at baseline and at the end of FTD/TPI therapy) with multifocal synchronous metastases and a longstanding history of extensive hematological events during previous treatments. Finally, this 62-year-old male patient was treated for 10 months with FTD/TPI by consecutive alteration of treatment parameters: (i) initial daily dose reduction to 80 mg (72% of the recommended dose), (ii) 20 days dose delay, (iii) a second and later third dose reduction to 70 mg and 60 mg (about 64% and 55%, respectively, of the recommended dose), and (iv) 30 µg per day of granulocyte colony-stimulating factor administration first for 3 days, and later for 5 days, for each treatment cycle...
January 2018: Case Reports in Oncology
Yoshinori Munemoto, Mitsuro Kanda, Koji Oba, Ho Min Kim, Hiroyoshi Takemoto, Tadamichi Denda, Naoki Nagata, Nao Takano, Mutsumi Fukunaga, Masato Kataoka, Yukihiko Tokunaga, Junichi Sakamoto, Hideyuki Mishima
PURPOSE: Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted...
March 5, 2018: Cancer Chemotherapy and Pharmacology
Andrew Graham Hill, Michael Findlay, Matthew Burge, Christopher Jackson, Pilar García Alfonso, Leslie Samuel, Vinod Ganju, Meinolf Karthaus, Alessio Amatu, Mark Jeffery, Maria Di Bartolomeo, John Bridgewater, Andrew L Coveler, Manuel Hidalgo, Amy V Kapp, Roxana Sufan, Bruce McCall, William Hanley, Elicia Penuel, Andrea Pirzkall, Josep Tabernero
PURPOSE: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. EXPERIMENTAL DESIGN: mCRC patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. RESULTS: Of 134 randomized patients, 98 were RAS ex2/3 wild-type...
March 5, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sara García Gil, Ruth Ramos Díaz, Gloria Julia Nazco Casariego, Marta Llanos Muñoz, Maria Micaela Viña Romero, Braulio Martín Calero, Jose Antonio Pérez Pérez, Fernando Gutiérrez Nicolás
BACKGROUND AND OBJECTIVES: Evaluate the relationship between the presence of polymorphisms in genes involved in the pharmacodynamics of irinotecan (UGT1A, SLCO1B1, ABCB1 and ABCC2) and the safety of irinotecan in the treatment of metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Prospective observational, single-centre study of 30 months duration, which included patients diagnosed with mCRC treated with FOLFIRI was carried out. Toxicity was evaluated in each treatment cycle according to the Common Terminology Criteria for Adverse Events (CTCAE) v...
February 27, 2018: Medicina Clínica
Yiyi Zhang, Zongbin Xu, Yanwu Sun, Pan Chi, Xingrong Lu
Introduction: Kallikrein 11 (KLK11) plays a crucial role in drug-resistance to oxaliplatin (L-OHP) in the treatment of metastatic colorectal cancer (mCRC). The study aimed to investigate the role of KLK11 in chemoresistance, and to clarify the mechanism underlying reverse of L-OHP resistance by knockdown of KLK11. Materials and Methods: Resistance to oxaliplatin was induced in HCT-8 (HCT-8/L-OHP) colorectal adenocarcinoma cell lines by exposing cells to increasing concentrations of L-OHP...
2018: OncoTargets and Therapy
Teresa Di Desidero, Paola Orlandi, Anna Fioravanti, Chiara Cremolini, Fotios Loupakis, Federica Marmorino, Carlotta Antoniotti, Gianluca Masi, Sara Lonardi, Francesca Bergamo, Vittorina Zagonel, Alfredo Falcone, Guido Bocci
The aim of the present study was to assess the pharmacokinetics (PK) of metronomic capecitabine and its metabolites in a population of refractory metastatic colorectal cancer (mCRC) patients. Thirty-four patients (M/F, 22/12) with a diagnosis of mCRC received capecitabine 800 mg p.o. twice a day and cyclophosphamide 50 mg/day p.o. Blood samples were collected at baseline, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h and 5 h at day 1 after capecitabine administration. Plasma concentrations of capecitabine and its metabolites were measured by high performance liquid chromatography and the main PK parameters were calculated...
February 27, 2018: Investigational New Drugs
Wen-Chi Chou, Min-Hsien Wu, Pei-Hung Chang, Hung-Chih Hsu, Gwo-Jyh Chang, Wen-Kuan Huang, Chiao-En Wu, Jason Chia-Hsun Hsieh
Background: There is an urgency to develop robust prognostic biomarkers for metastatic colorectal cancer (mCRC) patients receiving chemotherapy. The current study aimed to examine the prognostic significance of circulating tumour cells (CTCs) and to develop a prognostic model incorporating CTCs in predicting the outcomes of mCRC patients treated with chemotherapy. Methods: Our study prospectively enrolled 55 mCRC patients who had undergone palliative chemotherapy between 2011 and 2014. Baseline CTCs and clinicopathological variables predictive of survival outcome were identified using univariate analysis...
2018: International Journal of Biological Sciences
Gonzalo Tapia Rico, Timothy J Price
Atezolizumab is a fully humanized, engineered monoclonal antibody (MAb) of IgG1 isotype that specifically targets programmed death ligand 1 (PD-L1), a key molecule in the cancer-immunity pathway. Atezolizumab is currently approved for the treatment of metastatic non-small-cell lung cancer (NSCLC) and advanced urothelial carcinomas. Areas covered: In this review, we will present the available (early phase clinical trials) data supporting the efficacy of atezolizumab for the treatment of metastatic colorectal cancer (mCRC)...
February 23, 2018: Expert Opinion on Biological Therapy
Sheik Emambux, Gaelle Tachon, Audelaure Junca, David Tougeron
Introduction Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and clinical outcome has improved substantially during the last two decades with targeted therapies. The immune system has a major role in cancers, especially the CD8+ T cells specific to tumor antigens. However, tumors can escape immune response by different mechanisms including upregulation of inhibitory immune checkpoint receptors, such as well-known Programmed cell Death protein-1 (PD-1)/Programmed cell Death Ligand 1 (PD-L1) interaction, leading CD8+ T cells to a state of anergy...
February 22, 2018: Expert Opinion on Biological Therapy
Hironaga Satake, Akihito Tsuji, Masato Nakamura, Masaaki Ogawa, Takeshi Kotake, Yukimasa Hatachi, Hisateru Yasui, Akinori Takagane, Yoshihiro Okita, Kumi Nakamura, Toshihide Onikubo, Masahiro Takeuchi, Masashi Fujii
BACKGROUND: FOLFOXIRI is now regarded as the chemotherapy regimen that offers the best platform for the treatment of colorectal cancer. However, the safety and efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC). METHODS: Patients received combination therapy consisting of panitumumab (6 mg/kg on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m2 , and folinate (LV) 200 mg/m2 ] on day 1, followed by fluorouracil (5-FU) 3200 mg/m2 infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of RAS wild-type mCRC patients...
February 20, 2018: International Journal of Clinical Oncology
D Arnold, G W Prager, A Quintela, A Stein, S Moreno, N Mounedji, J Taieb
Background: The optimal chemotherapeutic regimen for use beyond the second-line for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials and methods: We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC...
February 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Chiara Cremolini, Carlotta Antoniotti, Sara Lonardi, Giuseppe Aprile, Francesca Bergamo, Gianluca Masi, Roberta Grande, Giuseppe Tonini, Claudia Mescoli, Giovanni Gerardo Cardellino, Luigi Coltelli, Lisa Salvatore, Domenico Cristiano Corsi, Cristiana Lupi, Donatello Gemma, Monica Ronzoni, Emanuela Dell'Aquila, Federica Marmorino, Francesca Di Fabio, Maria Laura Mancini, Lorenzo Marcucci, Gabriella Fontanini, Vittorina Zagonel, Luca Boni, Alfredo Falcone
Importance: The combination of a triple-drug chemotherapy regimen with an anti-epidermal growth factor receptor (EGFR) agent as a first-line treatment of metastatic colorectal cancer (mCRC) showed promising activity along with safety concerns in single-arm phase 2 trials. The role of maintenance following chemotherapy and anti-EGFR and the optimal regimen to be adopted are not established. Objectives: To evaluate the activity and safety of cetuximab plus modified FOLFOXIRI (mFOLFOXIRI) and explore the role of maintenance with cetuximab or bevacizumab in RAS and BRAF wild-type mCRC...
February 15, 2018: JAMA Oncology
Claudiu Hopirtean, Viorica Nagy
Colorectal cancer is one of the most frequent forms of cancer both in men and women, and patients with metastatic disease are now being exposed to an increasing number of therapeutic agents to improve the survival outcomes. Vascular endothelial growth factor (VEGF) has o key role in the tumor growth and spreading. The approval of 4 agents that target angiogenic pathways in combination with standard chemotherapy improve overall and progression free survival and offer many opportunities to sequencing the treatment in patients with metastatic colorectal cancer (mCRC)...
2018: Clujul Medical (1957)
Bingjun Bai, Lina Shan, Binbin Xie, Xuefeng Huang, Weifang Mao, Xiaowei Wang, Da Wang, Hongbo Zhu
KRAS mutations serve a function in tumorigenesis of colorectal cancer (CRC) and guide the use of targeted drugs. However, the prognostic value of KRAS mutations and their subtypes remain controversial. The present study aimed to investigate the correlations between KRAS mutations and clinicopathological characteristics, and their prognostic significance in Chinese patients with metastatic CRC (mCRC). A total of 135 patients with mCRC were analyzed for KRAS mutations. Mutations in codon 12 and 13 were identified in 45 (33...
March 2018: Oncology Letters
Gerardo Rosati, Carmine Pinto, Francesca Di Fabio, Silvana Chiara, Ivan R Lolli, Enzo M Ruggeri, Libero Ciuffreda, Raimondo Ferrara, Lorenzo Antonuzzo, Daniela Adua, Patrizia Racca, Domenico Bilancia, Elena Benincasa, Maria Elena Stroppolo, Francesco Di Costanzo
OBJECTIVES: The influence of age (<70 years and ≥70 years) was retrospectively studied on the quality of life (QoL), incidence of side effects (including skin reactions) and efficacy of chemotherapy plus cetuximab in patients with KRAS wild type (WT) metastatic colorectal cancer (mCRC). METHODS: 225 patients of the Observed study (PS 0-1) were retrieved based on age (< 70 and ≥70 years) and evaluated through EORTC QLQ-C30 and DLQI questionnaires...
February 9, 2018: Journal of Geriatric Oncology
Alfonso Reginelli, Alfredo Clemente, Claudia Cardone, Fabrizio Urraro, Andrea Izzo, Erika Martinelli, Teresa Troiani, Fortunato Ciardiello, Luca Brunese, Salvatore Cappabianca
AIM: Regorafenib induces radiological changes in liver metastasis among patients with metastatic colorectal cancer (mCRC). The standard criteria used to evaluate solid tumor response (Response Evaluation Criteria in Solid Tumors) may be limited in assessing response to biologic agents with anti-angiogenic action. PATIENTS & METHODS: A total of 67 hepatic lesions in 32 selected patients were analyzed to evaluate tumor attenuation as measured by Hounsfield unit (HU) and size changes...
February 13, 2018: Future Oncology
Clara Montagut, Guillem Argilés, Fortunato Ciardiello, Thomas T Poulsen, Rodrigo Dienstmann, Michael Kragh, Scott Kopetz, Trine Lindsted, Cliff Ding, Joana Vidal, Jenifer Clausell-Tormos, Giulia Siravegna, Francisco J Sánchez-Martín, Klaus Koefoed, Mikkel W Pedersen, Michael M Grandal, Mikhail Dvorkin, Lucjan Wyrwicz, Ana Rovira, Antonio Cubillo, Ramon Salazar, Françoise Desseigne, Cristina Nadal, Joan Albanell, Vittorina Zagonel, Salvatore Siena, Guglielmo Fumi, Giuseppe Rospo, Paul Nadler, Ivan D Horak, Alberto Bardelli, Josep Tabernero
Importance: Acquired resistance to anti-EGFR therapy (epidermal growth factor receptor) is frequently due to RAS and EGFR extracellular domain (ECD) mutations in metastatic colorectal cancer (mCRC). Some anti-EGFR-refractory patients retain tumor EGFR dependency potentially targetable by agents such as Sym004, which is a mixture of 2 nonoverlapping monoclonal antibodies targeting EGFR. Objective: To determine if continuous blockade of EGFR by Sym004 has survival benefit...
February 8, 2018: JAMA Oncology
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