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Zhiwei Sun, Xicheng Wang, Jun Jia, Chuanling Liu, Xiaodong Zhang, Lin Shen
OBJECTIVE: To analyze the relationship between primary tumor location and clinical response of chemotherapy in patients with metastatic colorectal cancer(mCRC). METHODS: Clinical data of 721 mCRC patients who received first-line and second-line chemotherapy in Peking University Cancer Hospital between January 1996 and December 2011 were collected. All the patients were divided into 5 groups according to primary tumor location: ileocecum in 61 patients(8.5%), ascending colon or hepatic flexure in 126 patients (17...
October 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Egor Bobrov, Natalia Skobeleva, Diana Restifo, Natalya Beglyarova, Kathy Q Cai, Elizabeth Handorf, Kerry Campbell, David A Proia, Vladimir Khazak, Erica A Golemis, Igor Astsaturov
The lack of effective treatment modalities is a major problem in pancreatic cancer (PCa), a devastating malignancy that is nearly universally driven by the "undruggable" KRAS and TP53 cancer genes. Poor tumor tissue penetration is the major source of resistance in pancreatic cancer where chemotherapy is the mainstay of treatment. In this study we exploited the selective tumor-targeting properties of the heat shock 90 protein inhibitors as the vehicle for drug delivery to pancreatic tumor tissues. STA-12-8666 is a novel esterase-cleavable conjugate of an HSP90i and a topoisomerase I inhibitor, SN-38...
October 13, 2016: Oncotarget
Motoo Nomura, Satoru Iwasa, Takahiro Tsushima, Ken Kato, Hirofumi Yasui, Narikazu Boku, Manabu Muto, Kei Muro
PURPOSE: The survival benefit of chemotherapy (CTx) compared with best supportive care (BSC) is unclear in patients with recurrent or metastatic esophageal squamous cell carcinoma (R/M-ESCC) previously treated with fluorouracil (FU), platinum (PT), and taxane (TAX). PATIENTS AND METHODS: The data of 283 consecutive patients with R/M-ESCC, who could not tolerate or whose tumor was refractory to all three agents (FU, PT, and TAX) between March 2003 and November 2014, were retrospectively reviewed...
October 24, 2016: Cancer Chemotherapy and Pharmacology
Andreas Keil, Sean R Hall, Meike Körner, Martin Herrmann, Ralph A Schmid, Steffen Frese
BACKGROUND: Since the precise mechanism for the pathogenesis of systemic lupus erythematosus (SLE) is unknown, no targeted therapies in addition to immunosuppression are available so far. We recently demonstrated that administration of the topoisomerase I (topo I) inhibitor irinotecan at extremely low concentrations reversed established lupus nephritis in NZB/NZW mice. While profound immunosuppression was absent, we proposed changes in DNA relaxation and anti-double-stranded (ds)DNA antibody binding as the underlying mechanism...
October 22, 2016: Arthritis Research & Therapy
Mark R Gilbert, Stephanie L Pugh, Ken Aldape, A Gregory Sorensen, Tom Mikkelsen, Marta Penas-Prado, Felix Bokstein, Young Kwok, R Jeffrey Lee, Minesh Mehta
Angiogenesis, a hallmark of glioblastoma, can potentially be targeted by inhibiting the VEGF pathway using bevacizumab, a humanized monoclonal antibody against VEGF-A. This study was designed to determine the efficacy and safety of these regimens in the cooperative group setting. Eligibility included age ≥18, recurrent or progressive GBM after standard chemoradiation. Treatment was intravenous bevacizumab 10 mg/kg and either irinotecan (CPT) 125 mg/m(2) every 2 weeks or temozolomide (TMZ) 75-100 mg/m(2) day 1-21 of 28 day cycle...
October 21, 2016: Journal of Neuro-oncology
Bronwen J Mayo, Andrea M Stringer, Joanne M Bowen, Emma H Bateman, Dorothy M Keefe
PURPOSE: A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention...
October 21, 2016: Cancer Chemotherapy and Pharmacology
Hongfang Zhang, Conghua Xie, Jing Yue, Zhenzhen Jiang, Rongjing Zhou, Ruifei Xie, Yan Wang, Shixiu Wu
Previous studies on the mechanisms underlying ESCC (esophageal squamous cell carcinoma) chemoresistance only focused on tumor cells while tumor microenvironment has been completely ignored. Our study aimed to clarify the effect of CAFs (cancer-associated fibroblasts), one major component of tumor microenvironment, on the chemoresistance of ESCC. By primary culture, two pairs of CAFs and matched NFs (normal fibroblasts) were isolated from tumor tissues of ESCC patients and matched normal esophageal epithelial tissues, respectively...
October 21, 2016: Molecular Carcinogenesis
Mohamed Bouchahda, Valérie Boige, Denis Smith, Abdoulaye Karaboué, Michel Ducreux, Mohamed Hebbar, Céline Lepère, Christian Focan, Rosine Guimbaud, Pasquale Innominato, Sameh Awad, Carlos Carvalho, Salvatore Tumolo, Stephanie Truant, Thierry De Baere, Denis Castaing, Philippe Rougier, Jean-François Morère, Julien Taieb, René Adam, Francis Lévi
BACKGROUND: Early tumour shrinkage has been associated with improved survival in patients receiving cetuximab-based systemic chemotherapy for liver metastases from colorectal cancer (LM-CRC). We tested this hypothesis for previously treated LM-CRC patients receiving cetuximab (500 mg/m(2)) and triplet hepatic artery infusion (HAI) within European trial OPTILIV. METHODS: Irinotecan (180 mg/m(2)), 5-fluorouracil (2800 mg/m(2)) and oxaliplatin (85 mg/m(2)) were given as chronomodulated or conventional delivery...
October 17, 2016: European Journal of Cancer
J L Cubero, P Escudero, A Yubero, P Millán, M A Sagredo, C Colás
No abstract text is available yet for this article.
October 2016: Journal of Investigational Allergology & Clinical Immunology
H A Marsman, M G Besselink
- The incidence of pancreatic cancer is increasing due to the ageing population among other things, while 5-year survival has improved in the past two decades from 3 to 7%.- In case of biliary obstruction due to pancreatic cancer, biliary drainage before surgery or ablative therapy using a covered metal stent instead of plastic reduces the rate of complications.- In patients with metastasized pancreatic cancer a combination of folinic acid, fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) results in improved survival...
2016: Nederlands Tijdschrift Voor Geneeskunde
Hironobu Tsubouchi, Nobuhiro Matsumoto, Shigehisa Yanagi, Yasuji Arimura, Masamitsu Nakazato
Sepsis is a life-threatening condition caused by the inflammatory response to invading organisms. Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is used to reduce blood endotoxin levels and modulate circulating inflammatory cytokine levels in sepsis patients. Here we report that severe sepsis caused by an infection of the gram-negative bacterium Pantoea agglomerans in a patient with small cell lung carcinoma was treated successfully with antibiotics and PMX-DHP. The patient, a 49-year-old Japanese male smoker whose condition was complicated with hyponatremia due to SIADH (syndrome of inappropriate secretion of antidiuretic hormone), rapidly developed sepsis and disseminated intravascular coagulation (DIC) after the administration of cisplatin and irinotecan...
2016: Respiratory Medicine Case Reports
Taehwan Park, Chang-Ju Choi, Yeera Choi, Dong-Churl Suh
Cetuximab is a novel biological agent with superior therapeutic efficacy for colorectal cancer treatment. This study aimed to systematically review the existing evidence related to the cost-effectiveness of cetuximab. Areas covered: Using Medline and Cochrane Database of Systematic Reviews, a total of 12 articles were identified. Previous studies have shown mixed results on the cost-effectiveness of first-line cetuximab combined with FOLFIRI (5-Fluorouracil, leucovorin, irinotecan). However, cetuximab-irinotecan therapy as third-line treatment has consistently been found to be cost-ineffective compared to best supportive care or no third-line therapy...
October 18, 2016: Expert Review of Pharmacoeconomics & Outcomes Research
Zhao-Wei Zou, Hai-Jin Chen, Jin-Long Yu, Zong-Hai Huang, Shun Fang, Xiao-Hua Lin
Chemotherapy is one of the most commonly used therapeutic strategies for metastatic colon cancer. However, the development of resistance to chemotherapeutic agents limits their application in clinical use. The underlying mechanisms of this resistance development require further elucidation. The current study investigated the effects of connexin43 (Cx43) gap junctions on 5‑fluorouracil (5‑FU), oxaliplatin and irinotecan in colon cancer cells. Three different methods were used to manipulate Cx43 gap junction function: i) Cell culture at different densities; ii) pretreatment with a Cx43 specific inhibitor or enhancer; and iii) Cx43 gene knock‑down...
October 6, 2016: Molecular Medicine Reports
Carmine Pinto, Francesca Di Fabio, Gerardo Rosati, Ivan R Lolli, Enzo M Ruggeri, Libero Ciuffreda, Daris Ferrari, Giovanni Lo Re, Giovanni Rosti, Paolo Tralongo, Raimondo Ferrara, Oscar Alabiso, Silvana Chiara, Giovanni P Ianniello, Antonio Frassoldati, Domenico Bilancia, Giovanna A Campanella, Carlo Signorelli, Patrizia Racca, Elena Benincasa, Maria Elena Stroppolo, Francesco Di Costanzo
Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real-world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first-line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ-C30...
October 17, 2016: Cancer Medicine
Rohan C Parikh, Xianglin L Du, Robert O Morgan, David R Lairson
BACKGROUND: Over the last decade, multiple chemotherapies/targeted biologics have been approved for metastatic colorectal cancer (mCRC). However, evidence is limited with regards to the array of treatments received by mCRC patients. OBJECTIVE: This study examines treatment sequences (first- to third-line chemotherapy/targeted biologics) and the factors associated with first-line targeted biologics and common treatment sequences for elderly mCRC patients treated in a community setting...
March 2016: Drugs—Real World Outcomes
Ji-Youn Han, Geon Kook Lee, Kun Young Lim, Young Ju Lee, Byung Ho Nam, Jin Soo Lee
Purpose: We evaluated the clinical utility of excision repair cross-complementation group 1 (ERCC1) expression as a predictive biomarker for platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eligible patients were randomly assigned to the GP (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 1 every 3 weeks) or IP (irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 every 3 weeks) arm. The primary goal of this study was to compare the response rate (RR) of the GP and IP arms according to the ERCC1 expression level...
October 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
M Moore, S Gill, T Asmis, S Berry, R Burkes, K Zbuk, T Alcindor, A Jeyakumar, T Chan, S Rao, J Spratlin, P A Tang, J Rothenstein, E Chan, J Bendell, F Kudrik, J Kauh, S Tang, L Gao, S R P Kambhampati, F Nasroulah, L Yang, N Ramdas, P Binder, E Strevel
BACKGROUND: Icrucumab and ramucirumab are recombinant human IgG1 monoclonal antibodies that bind VEGF receptors 1 and 2 (VEGFR-1 and -2), respectively. This randomized phase II study evaluated the antitumor activity and safety of icrucumab and ramucirumab each in combination with mFOLFOX-6 in patients with metastatic colorectal cancer after disease progression on first-line therapy with a fluoropyrimidine and irinotecan. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive mFOLFOX-6 alone (mFOLFOX-6) or in combination with ramucirumab 8 mg/kg IV (RAM+mFOLFOX-6) or icrucumab 15 mg/kg IV (ICR+mFOLFOX-6) every 2 weeks...
October 11, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
David S Hong, Van K Morris, Badi El Osta, Alexey V Sorokin, Filip Janku, Siqing Fu, Michael J Overman, Sarina Piha-Paul, Vivek Subbiah, Bryan Kee, Apostolia Tsimberidou, David Fogelman, Jorge Bellido, Imad Shureiqi, Helen Huang, Johnique Atkins, Gabi Tarcic, Nicolas Sommer, Richard Lanman, Funda Meric-Bernstam, Scott Kopetz
In vitro, EGFR inhibition, combined with the BRAF inhibitor vemurafenib, causes synergistic cytotoxicity for BRAFV600E metastatic colorectal cancer (mCRC), further augmented by irinotecan. The safety and efficacy of vemurafenib, irinotecan, and cetuximab in BRAF-mutated malignancies are not defined. In this 3+3 phase I study, patients with BRAFV600E advanced solid cancers received cetuximab and irinotecan with escalating doses of vemurafenib. Nineteen patients (18 with mCRC, 1 with appendiceal cancer) were enrolled...
October 11, 2016: Cancer Discovery
Xiaofu Zhu, Yoo-Joung Ko, Scott Berry, Keya Shah, Esther Lee, Kelvin Chan
BACKGROUND: It is unclear which regimen is the most efficacious among the available therapies for advanced gastric cancer in the second-line setting. We performed a network meta-analysis to determine their relative benefits. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and American Society of Clinical Oncology abstracts up to June 2014 to identify phase III RCTs on advanced gastric cancer in the second-line setting...
October 8, 2016: Gastric Cancer
Sabine Tejpar, Sebastian Stintzing, Fortunato Ciardiello, Josep Tabernero, Eric Van Cutsem, Frank Beier, Regina Esser, Heinz-Josef Lenz, Volker Heinemann
Importance: Metastatic colorectal cancer (mCRC) is heterogeneous, and primary tumors arising from different regions of the colon are clinically and molecularly distinct. Objective: To examine the prognostic and predictive value of primary tumor location in patients with RAS wild-type (wt) mCRC treated with first-line fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus cetuximab in the Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (CRYSTAL) trial and FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab as First-Line Treatment For Patients With Metastatic Colorectal Cancer (FIRE-3) trial...
October 10, 2016: JAMA Oncology
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