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https://www.readbyqxmd.com/read/28817838/pharmacogenetic-determinants-of-outcomes-on-triplet-hepatic-artery-infusion-and-intravenous-cetuximab-for-liver-metastases-from-colorectal-cancer-european-trial-optiliv-nct00852228
#1
Francis Lévi, Abdoulaye Karaboué, Raphaël Saffroy, Christophe Desterke, Valerie Boige, Denis Smith, Mohamed Hebbar, Pasquale Innominato, Julien Taieb, Carlos Carvalho, Rosine Guimbaud, Christian Focan, Mohamed Bouchahda, René Adam, Michel Ducreux, Gérard Milano, Antoinette Lemoine
BACKGROUND: The hepatic artery infusion (HAI) of irinotecan, oxaliplatin and 5-fluorouracil with intravenous cetuximab achieved outstanding efficacy in previously treated patients with initially unresectable liver metastases from colorectal cancer. This planned study aimed at the identification of pharmacogenetic predictors of outcomes. METHODS: Circulating mononuclear cells were analysed for 207 single-nucleotide polymorphisms (SNPs) from 34 pharmacology genes...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28817371/phase-i-ii-trial-of-labetuzumab-govitecan-anti-ceacam5-sn-38-antibody-drug-conjugate-in-patients-with-refractory-or-relapsing-metastatic-colorectal-cancer
#2
Efrat Dotan, Steven J Cohen, Alexander N Starodub, Christopher H Lieu, Wells A Messersmith, Pamela S Simpson, Michael J Guarino, John L Marshall, Richard M Goldberg, J Randolph Hecht, William A Wegener, Robert M Sharkey, Serengulam V Govindan, David M Goldenberg, Jordan D Berlin
Purpose The objectives were to evaluate dosing schedules of labetuzumab govitecan, an antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for tumor delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with relapsed or refractory metastatic colorectal cancer. Patients and Methods Eligible patients with at least one prior irinotecan-containing therapy received labetuzumab govitecan once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817187/second-line-treatment-in-patients-with-pancreatic-ductal-adenocarcinoma-a-meta-analysis
#3
Mohamad Bassam Sonbol, Belal Firwana, Zhen Wang, Diana Almader-Douglas, Mitesh J Borad, Issam Makhoul, Ramesh K Ramanathan, Daniel H Ahn, Tanios Bekaii-Saab
BACKGROUND: There are limited therapeutic options for treatment-refractory pancreatic ductal adenocarcinoma (PDAC), with a paucity of data to support the best option after progression on gemcitabine-based regimens. The authors performed a meta-analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan formulations to a fluoropyrimidine (FP) after first-line treatment progression in patients with PDAC. METHODS: Different databases, including PubMed, EMBASE, and Cochrane, were searched to identify randomized controlled trials comparing FP monotherapy versus FP combination therapy that included either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in patients with PDAC who progressed after first-line treatment...
August 17, 2017: Cancer
https://www.readbyqxmd.com/read/28814865/in-vitro-and-in-vivo-evaluation-of-sn-38-nanocrystals-with-different-particle-sizes
#4
Min Chen, Wanqing Li, Xun Zhang, Ye Dong, Yabing Hua, Hui Zhang, Jing Gao, Liang Zhao, Ying Li, Aiping Zheng
7-Ethyl-10-hydroxycamptothecin (SN-38) is a potent broad-spectrum antitumor drug derived from irinotecan hydrochloride (CPT-11). Due to its poor solubility and instability of the active lactone ring, its clinical use is significantly limited. As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have attracted increasing attention. In order to solve these problems and evaluate the antitumor effect of SN-38 in vitro and in vivo, two nanocrystals with markedly different particle sizes were prepared...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28814275/randomized-study-comparing-full-dose-monotherapy-s-1-followed-by-irinotecan-and-reduced-dose-combination-therapy-s-1-oxaliplatin-followed-by-s-1-irinotecan-as-initial-therapy-for-older-patients-with-metastatic-colorectal-cancer-nordic-9
#5
Stine Braendegaard Winther, Pia Österlund, Åke Berglund, Bengt Glimelius, Camilla Qvortrup, Halfdan Sorbye, Per Pfeiffer
BACKGROUND: Metastatic colorectal cancer (mCRC) is a disease of older age, but there is a relative lack of knowledge about effects of chemotherapy in older patients as they are under-represented in clinical trials. Little data can guide whether the strategy in older mCRC patients should be a sequential full-dose monotherapy chemotherapy approach or a dose-reduced combination chemotherapy approach. The oral 5FU prodrug S-1 seems to have less side effects than capecitabine and should be an optimal drug for older patients, but few data are available...
August 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28807738/observed-benefit-and-safety-of-aflibercept-in-elderly-patients-with-metastatic-colorectal-cancer-an-age-based-analysis-from-the-randomized-placebo-controlled-phase-iii-velour-trial
#6
Paul Ruff, Eric Van Cutsem, Radek Lakomy, Jana Prausova, Guy A van Hazel, Vladimir M Moiseyenko, Karen Soussan-Lazard, Emmanuelle Dochy, Emmanuelle Magherini, Teresa Macarulla, Demetris Papamichael
OBJECTIVES: Aflibercept (ziv-aflibercept) significantly improves progression-free (PFS) and overall survival (OS) when added to 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), compared with FOLFIRI alone, in patients with metastatic colorectal cancer previously treated with oxaliplatin-based therapy. This subset analysis of the VELOUR study investigates aflibercept plus FOLFIRI versus placebo plus FOLFIRI according to age. METHODS: Efficacy and safety were analyzed by treatment arm and age (≥ or <65years)...
August 12, 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/28807246/hepatic-intra-arterial-injection-of-irinotecan-drug-eluting-beads-debiri-for-patients-with-unresectable-colorectal-liver-metastases-a%C3%A2-systematic-review
#7
REVIEW
Olaguoke Akinwande, Meaghan Dendy, Johannes M Ludwig, Hyun S Kim
PURPOSE: To systematically review the safety and efficacy of transarterial drug-eluting beads, irinotecan (DEBIRI) for the treatment of pretreated patients with unresectable colorectal liver metastases (CRLM). METHODS: A systematic search of the current literature was conducted to extract publications reporting on the use of DEBIRI for CRLM. Data on the safety and efficacy was extracted and tabulated. Weighted average values (WAV) were calculated for each variable to provide a single value representing the pooled safety and efficacy data...
September 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28804517/update-on-the-role-of-nanoliposomal-irinotecan-in-the-treatment-of-metastatic-pancreatic-cancer
#8
REVIEW
Fnu Asad Ur Rahman, Saeed Ali, Muhammad Wasif Saif
Median survival for patients with metastatic pancreatic cancer (MPC) treated with combination chemotherapeutic agents such as gemcitabine-based regimens and FOLFIRINOX is currently less than 12 months. This highlights the need for more efficacious first-line, as well as second-line therapies. Nanoliposomal irinotecan, in combination with 5-fluorouracil (5-FU)/folinic acid has recently been assessed as second-line therapy after initial gemcitabine-based therapy. It is the first, second-line treatment approved by the US Food and Drug Administration to treat patients with MPC based on results of the NAnoliPOsomaL Irinotecan (NAPOLI-1) study, which showed that this regimen significantly prolonged progression-free survival (3...
July 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28803383/synchronous-colorectal-liver-metastases-focus-on-the-elderly-an-effectiveness-study-from-routine-care
#9
Markus Albertsmeier, Andrea Engel, Markus O Guba, Sebastian Stintzing, Tobias S Schiergens, Gabriele Schubert-Fritschle, Dieter Hölzel, Jens Werner, Martin K Angele, Jutta Engel
PURPOSE: The goal of this study was to analyze the use and the effectiveness of both surgery and different chemotherapies in patients with synchronous colorectal liver metastases (CLMs) ≥70 years compared to younger patients. METHODS: Survival was analyzed in 456 patients (24.3% ≥70 years) treated for CLM in a single center using Kaplan-Meier estimation of overall survival (OS), calculation of relative survival as estimate for disease-specific survival, and a Cox regression model...
August 12, 2017: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/28801547/early-changes-in-plasma-dna-levels-of-mutant-kras-as-a-sensitive-marker-of-response-to-chemotherapy-in-pancreatic-cancer
#10
Marzia Del Re, Caterina Vivaldi, Eleonora Rofi, Enrico Vasile, Mario Miccoli, Chiara Caparello, Paolo Davide d'Arienzo, Lorenzo Fornaro, Alfredo Falcone, Romano Danesi
Pancreatic cancer (PDAC) is still lacking of reliable markers to monitor tumor response. CA 19-9 is the only biomarker approved, despite it has several limitations in sensitivity and specificity. Since mutations of KRAS occur in more than 90% of tumors, its detection in circulating free tumor DNA (cftDNA) could represent a biomarker to monitor chemotherapy response. Twenty-seven advanced PDAC patients given first-line 5-fluorouracil, irinotecan and oxaliplatin or gemcitabine and nab-paclitaxel were enrolled...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801072/irinotecan-chemotherapy-induced-intestinal-oxidative-stress-underlying-causes-of-disturbed-mucosal-water-and-electrolyte-transport
#11
Kaïs Rtibi, Slimen Selmi, Dhekra Grami, Hichem Sebai, Mohamed Amri, Lamjed Marzouki
Irinotecan, a chemotherapy drug, can cause acute diarrhea immediately after administration. Hence, the present study was designed to investigate the gastrointestinal (GI) disturbances after an intraperitoneal (IP) administration of irinotecan in rats.Twenty Wistar rats were separated into two groups of ten. Group A was considered as a control group (NaCl, 0.9%). Group B was treated with irinotecan at a single dose of 200mgkg(-1). The rats were observed for defecation. For the enteropooling test, the animals were sacrificed by decapitation 1h post-treatment...
July 23, 2017: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/28800641/high-rbm3-expression-is-associated-with-an-improved-survival-and-oxaliplatin-response-in-patients-with-metastatic-colorectal-cancer
#12
Christina Siesing, Halfdan Sorbye, Anca Dragomir, Per Pfeiffer, Camilla Qvortrup, Fredrik Pontén, Karin Jirström, Bengt Glimelius, Jakob Eberhard
BACKGROUND: High expression of the RNA-binding motif protein 3 (RBM3) has been shown to correlate, with prolonged survival in several malignant diseases and with the benefit of platinum-based chemotherapy in ovarian cancer. The aim of this study was to evaluate RBM3 in metastatic colorectal cancer (mCRC) as a prognostic factor for overall survival and in relation to benefit of first-line chemotherapy. METHODS: Immunohistochemical staining was conducted and evaluated in tumours from 455 mCRC patients...
2017: PloS One
https://www.readbyqxmd.com/read/28799048/irinotecan-monotherapy-as-third-line-or-later-treatment-in-advanced-gastric-cancer
#13
Akitaka Makiyama, Kohei Arimizu, Gen Hirano, Chinatsu Makiyama, Yuzo Matsushita, Tsuyoshi Shirakawa, Hirofumi Ohmura, Masato Komoda, Keita Uchino, Kyoko Inadomi, Shuji Arita, Hiroshi Ariyama, Hitoshi Kusaba, Yudai Shinohara, Miyuki Kuwayama, Tatsuhiro Kajitani, Hisanobu Oda, Taito Esaki, Koichi Akashi, Eishi Baba
BACKGROUND: Patients with advanced gastric cancer (AGC) are often treated with irinotecan monotherapy as salvage-line therapy. However, the survival benefit of this therapy remains to be elucidated. METHODS: Medical records of AGC patients who were treated with irinotecan monotherapy as salvage-line treatment in six institutions from 2007 to 2014 were reviewed. RESULTS: A total of 146 patients had prior fluoropyrimidine and taxane therapies, and 75...
August 10, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28797070/methyl-pyruvate-protects-a-normal-lung-fibroblast-cell-line-from-irinotecan-induced-cell-death-potential-use-as-adjunctive-to-chemotherapy
#14
Bernice Monchusi, Monde Ntwasa
The Warburg Effect, characterized by increased rate of glycolysis even under normoxic conditions, is one of the hallmarks of cancer. Relatively lower oxidative phosphorylation (OXPHOS) is also a characteristic feature in cancer cells. We hypothesized that interference with this phenomenon, by introducing exogenous pyruvate, would upset this cancer phenotype and boost the energy requirements of normal cells. We find that methyl pyruvate protects irinotecan-treated normal lung fibroblast cell line (MRC-5) probably by turning off the p53/p21 axis of the apoptotic pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28790841/relationship-between-ugt1a1-6-28-gene-polymorphisms-and-the-efficacy-and-toxicity-of-irinotecan-based-chemotherapy
#15
Yu Bai, Hai-Wei Wu, Xu Ma, Ying Liu, Yan-Hua Zhang
PURPOSE: A retrospective study was performed to analyze the relationship between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *6/*28 gene polymorphisms and adverse reactions associated with irinotecan (CPT-11)-based chemotherapy. The correlation between UGT1A1 polymorphisms and the clinical efficacy of CPT-11 was also analyzed, along with the influence of age and tumor type. PATIENTS AND METHODS: Patients administered a CPT-11-based regimen in the Beijing Cancer Hospital from April 2015 to September 2016 were included in our study (n=81)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28789891/design-synthesis-and-cytotoxic-activity-of-novel-7-substituted-camptothecin-derivatives-incorporating-piperazinyl-sulfonylamidine-moieties
#16
Cheng-Jie Yang, Zi-Long Song, Masuo Goto, Ying-Qian Liu, Kan-Yen Hsieh, Susan L Morris-Natschke, Yong-Long Zhao, Jun-Xiang Zhang, Kuo-Hsiung Lee
In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel 7-substituted CPT derivatives incorporating piperazinyl-sulfonylamidine moieties were designed, synthesized and evaluated for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB, and KB-VIN). All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, and were more potent than irinotecan. Remarkably, most of the compounds exhibited comparable cytotoxicity against the multidrug-resistant (MDR) KB-VIN and parental KB tumor cell lines, while irinotecan lost activity completely against KB-VIN...
July 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28768426/necrotising-fasciitis-in-a-patient-treated-with-folfiri-aflibercept-for-colorectal-cancer-a-case-report
#17
A Gonzaga-López, J Muñoz-Rodriguez, A Ruiz-Casado
Anti-angiogenics have become an important part of the treatment of several types of tumours such as ovarian, breast, lung and colorectal cancer. Necrotising fasciitis has been reported with bevacizumab but no cases have been reported with aflibercept, ramucirumab or regorafenib in patients with colorectal cancer. Necrotising fasciitis is a rare complication affecting one in 5000 bevacizumab users. We report the case of a 64-year-old man with stage IV rectosigmoid cancer under treatment with folinic acid, fluorouracil and irinotecan (FOLFIRI) and aflibercept, who developed a Fournier's gangrene...
August 3, 2017: Annals of the Royal College of Surgeons of England
https://www.readbyqxmd.com/read/28761750/european-medicines-agency-approval-summary-zaltrap-for-the-treatment-of-patients-with-oxaliplatin-resistant-metastatic-colorectal-cancer
#18
REVIEW
Stefan Cristian Stanel, Jan Sjöberg, Tomas Salmonson, Paolo Foggi, Mariapaola Caleno, Daniela Melchiorri, Iordanis Gravanis, Kyriaki Tzogani, Francesco Pignatti
On 1 February 2013, a marketing authorisation valid throughout the European Union was issued for aflibercept (Zaltrap) in combination with irinotecan/5-fluorouracil/folinic acid chemotherapy for the treatment of adults with metastatic colorectal cancer resistant to or progressive after an oxaliplatin-containing regimen. Aflibercept is a recombinant fusion protein which blocks the activation of vascular endothelial growth factor (VEGF) receptors and the proliferation of endothelial cells, acting as a soluble decoy receptor that binds to VEGF-A with higher affinity than its native receptors, as well as placental growth factor and VEGF-B...
2017: ESMO Open
https://www.readbyqxmd.com/read/28760399/tas-102-plus-bevacizumab-for-patients-with-metastatic-colorectal-cancer-refractory-to-standard-therapies-c-task-force-an-investigator-initiated-open-label-single-arm-multicentre-phase-1-2-study
#19
Yasutoshi Kuboki, Tomohiro Nishina, Eiji Shinozaki, Kentaro Yamazaki, Kohei Shitara, Wataru Okamoto, Takeshi Kajiwara, Toshihiko Matsumoto, Takahiro Tsushima, Nobuo Mochizuki, Shogo Nomura, Toshihiko Doi, Akihiro Sato, Atsushi Ohtsu, Takayuki Yoshino
BACKGROUND: In patients with heavily treated metastatic colorectal cancer, TAS-102-a combination of trifluridine and tipiracil-has shown a significant overall survival benefit compared with placebo. In preclinical models, TAS-102 plus bevacizumab has shown enhanced activity against colorectal cancer xenografts compared with that for either drug alone. In this phase 1/2 study, we assessed the activity and safety of TAS-102 plus bevacizumab. METHODS: We did this investigator-initiated, open-label, single-arm, multicentre, phase 1/2 trial of TAS-102 plus bevacizumab in four cancer centres in Japan...
July 28, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28753268/microscale-mass-spectrometry-analysis-of-extracellular-metabolites-in-live-multicellular-tumor-spheroids
#20
Mei Sun, Xiang Tian, Zhibo Yang
Extracellular compounds in tumors play critical roles in intercellular communication, tumor proliferation, and cancer cell metastasis. However, the lack of appropriate techniques leads to limited studies of extracellular metabolite. Here, we introduced a microscale collection device, the Micro-funnel, fabricated from biocompatible fused silica capillary. With a small probe size (∼25 μm), the Micro-funnel can be implanted into live multicellular tumor spheroids to accumulate the extracellular metabolites produced by cancer cells...
August 16, 2017: Analytical Chemistry
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