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Gemcitabine toxicity

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https://www.readbyqxmd.com/read/29145816/renal-failure-during-chemotherapy-renal-biopsy-for-assessing-subacute-nephrotoxicity-of-pemetrexed
#1
Maureen Assayag, Philippe Rouvier, Marion Gauthier, Ghania Costel, Philippe Cluzel, Lucile Mercadal, Gilbert Deray, Corinne Isnard Bagnis
BACKGROUND: Pemetrexed, a multitargeted antifolate cytotoxic agent, is currently used primarily in combination with cisplatin for metastatic non-small cell lung cancer and for malignant mesothelioma. Acute renal toxicity of pemetrexed has been recently described with polychemotherapy, in which the individual responsibility of each drug is difficult to establish. Only one recent report documents renal involvement in long-term exposed patients. CASE PRESENTATION: We report on a case of rapidly progressive nephropathy leading to the cessation of platinum salts and the secondary interruption of pemetrexed and bevacizumab...
November 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29129443/adjuvant-chemotherapy-with-or-without-bevacizumab-in-patients-with-resected-non-small-cell-lung-cancer-e1505-an-open-label-multicentre-randomised-phase-3-trial
#2
Heather A Wakelee, Suzanne E Dahlberg, Steven M Keller, William J Tester, David R Gandara, Stephen L Graziano, Alex A Adjei, Natasha B Leighl, Seena C Aisner, Jan M Rothman, Jyoti D Patel, Mark D Sborov, Sean R McDermott, Roman Perez-Soler, Anne M Traynor, Charles Butts, Tracey Evans, Atif Shafqat, Andrew E Chapman, Samer S Kasbari, Leora Horn, Suresh S Ramalingam, Joan H Schiller
BACKGROUND: Adjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC. METHODS: We did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC...
November 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29127277/dual-protein-kinase-and-nucleoside-kinase-modulators-for-rationally-designed-polypharmacology
#3
Kahina Hammam, Magali Saez-Ayala, Etienne Rebuffet, Laurent Gros, Sophie Lopez, Berengere Hajem, Martine Humbert, Emilie Baudelet, Stephane Audebert, Stephane Betzi, Adrien Lugari, Sebastien Combes, Sebastien Letard, Nathalie Casteran, Colin Mansfield, Alain Moussy, Paulo De Sepulveda, Xavier Morelli, Patrice Dubreuil
Masitinib, a highly selective protein kinase inhibitor, can sensitise gemcitabine-refractory cancer cell lines when used in combination with gemcitabine. Here we report a reverse proteomic approach that identifies the target responsible for this sensitisation: the deoxycytidine kinase (dCK). Masitinib, as well as other protein kinase inhibitors, such as imatinib, interact with dCK and provoke an unforeseen conformational-dependent activation of this nucleoside kinase, modulating phosphorylation of nucleoside analogue drugs...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29124327/a-phase-ii-study-of-biweekly-gemcitabine-and-carboplatin-in-completely-resected-stage-ib-iiia-non-small-cell-lung-cancer
#4
Reiko Sakurai, Yoshio Tomizawa, Akihiro Yoshii, Yosuke Miura, Hiroaki Tsurumaki, Kyoichi Kaira, Noriaki Sunaga, Osamu Kawashima, Takeshi Hisada, Masanobu Yamada, Ryusei Saito
PURPOSE: We conducted a prospective study to evaluate the efficacy and safety of biweekly gemcitabine and carboplatin combination treatment in patients with resected non-small cell lung cancer (NSCLC). METHODS: Patients with completely resected stage IB to IIIA NSCLC were treated with four cycles of gemcitabine (1000 mg/m(2), days 1 and 15) plus carboplatin [area under the time-concentration curve (AUC) 5 mg/mL/min, day 1] every 4 weeks as adjuvant chemotherapy...
November 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29121415/efficacy-and-safety-of-trametinib-in-japanese-patients-with-advanced-biliary-tract-cancers-refractory-to-gemcitabine
#5
Masafumi Ikeda, Tatsuya Ioka, Akira Fukutomi, Chigusa Morizane, Akiyoshi Kasuga, Hideaki Takahashi, Akiko Todaka, Takuji Okusaka, Caretha L Creasy, Shelby Gorman, Daniel J Felitsky, Mikiro Kobayashi, Fanghong Zhang, Junji Furuse
Gemcitabine-based therapy remains the mainstay of treatment for patients with biliary tract cancers (BTCs) with no second-line treatment(s) established yet. Aberrant activation of MAPK pathway in patients with BTC indicates its importance in BTC. Trametinib is a potent, highly selective, allosteric non-competitive inhibitor of MEK1/MEK2. In this Phase IIa open-label, single-arm study, we investigated efficacy and safety of trametinib in Japanese patients with advanced BTC refractory to gemcitabine-based therapy...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29119276/phase-ib-ii-study-of-gemcitabine-nab-paclitaxel-and-pembrolizumab-in-metastatic-pancreatic-adenocarcinoma
#6
Glen J Weiss, Lisa Blaydorn, Julia Beck, Kirsten Bornemann-Kolatzki, Howard Urnovitz, Ekkhard Schütz, Vivek Khemka
Background A single center phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab (GNP) to evaluate the safety and efficacy in metastatic pancreatic adenocarcinoma (PDAC) was conducted (NCT02331251). Methods PDAC patients (pts) with measurable disease, biopsy proven metastasis, adequate laboratory tests, and KPS ≥ 70% received GNP until progression or toxicity. Safety monitoring, RECIST 1.1, and irRECIST assessments were conducted. Response imaging was performed prior to cycle 4, then every 3 months...
November 8, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29114851/biweekly-cisplatin-and-gemcitabine-in-patients-advanced-biliary-tract-cancer
#7
Daniel H Ahn, Josh Reardon, Chul W Ahn, Manojkumar Bupathi, Sameh Mikhail, Christina Sing-Ying Wu, Tanios Bekaii-Saab
Treatment with cisplatin with gemcitabine (CG) demonstrates a survival benefit in patients with advanced biliary tract cancer (ABTC). However, the weekly administration can add significant toxicities that may prohibit prolonged treatment. Based on previous studies, we implemented a modified biweekly regimen of GC in an attempt to optimize the prescribed regimen with an improved toxicity profile, added convenience to patients while maintaining efficacy. Patients with ABTC were treated with fixed dose rate (FDR) gemcitabine (1000mg/m(2) /min) and cisplatin 20mg/m(2) on days 1 and 15 of every 28-day cycle...
November 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29114374/prevention-of-chemotherapy-induced-nephrotoxicity-in-children-with-cancer
#8
REVIEW
Fatemeh Ghane Sharbaf, Hamid Farhangi, Farahnak Assadi
Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL), ifosfamide (IFO), carboplatin, and methotrexate (MTX). Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI), tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS), and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels...
2017: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/29113401/optimal-adjuvant-chemotherapy-for-resected-pancreatic-adenocarcinoma-a-systematic-review-and-network-meta-analysis
#9
Jian-Bo Xu, Bin Jiang, Ya Chen, Fu-Zhen Qi, Jian-Huai Zhang, Hang Yuan
Adjuvant chemotherapy improves survival in patients with resected pancreatic cancer but the optimal regimen remains unclear. We aim to compare all possible adjuvant chemotherapy in terms of overall survival and toxic effects. Pubmed, Trial registries and Cochrane library databases for randomized controlled trials were searched until November 2016. Thirteen trials were included for network analysis and the hazard ratios (HRs) for survival and odds ratios for toxic effects were assessed via Aggregate Data Drug Information System software...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113399/dck-expression-a-potential-predictive-biomarker-in-the-adjuvant-gemcitabine-chemotherapy-for-biliary-tract-cancer-after-surgical-resection-results-from-a-phase-ii-study
#10
Sang Myung Woo, Kyong-Ah Yoon, Eun Kyung Hong, Weon Seo Park, Sung-Sik Han, Sang-Jae Park, Jungnam Joo, Eun Young Park, Ju Hee Lee, Yun-Hee Kim, Tae Hyun Kim, Woo Jin Lee
The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. This clinical phase II trial was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patients were started on intravenous infusions of gemcitabine 1000 mg/m(2) over 30 min on days 1, 8, and 15 of every 28-day cycle. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100455/clinical-validation-of-genetic-variants-associated-with-in-vitro-chemotherapy-related-lymphoblastoid-cell-toxicity
#11
Peter A Fasching, Lothar Häberle, Brigitte Rack, Liang Li, Alexander Hein, Arif B Ekici, Andre Reis, Michael P Lux, Julie M Cunningham, Matthias Ruebner, Gergory Jenkins, Brooke Fridley, Andreas Schneeweiss, Hans Tesch, Werner Lichtenegger, Tanja Fehm, Georg Heinrich, Mahdi Rezai, Matthias W Beckmann, Wolfgang Janni, Richard M Weinshilboum, Liewei Wang
Hematotoxicity is one of the major side effects of chemotherapy. The aim of this study was to examine the association between single nucleotide polymorphisms (SNPs) and hematotoxicity in breast cancer patients in a subset of patients of the SUCCESS prospective phase III chemotherapy study. All patients (n = 1678) received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by three cycles of docetaxel or docetaxel/gemcitabine, depending on randomization. Germline DNA was genotyped for 246 SNPs selected from a previous genome-wide association study (GWAS) in a panel of lymphoblastoid cell lines, with gemcitabine toxicity as the phenotype...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100289/chemosensitivity-directed-therapy-compared-to-dacarbazine-in-chemo-naive-advanced-metastatic-melanoma-a-multicenter-randomized-phase-3-decog-trial
#12
Selma Ugurel, Carmen Loquai, Patrick Terheyden, Dirk Schadendorf, Erika Richtig, Jochen Utikal, Ralf Gutzmer, Knuth Rass, Cord Sunderkötter, Annette Stein, Michael Fluck, Martin Kaatz, Uwe Trefzer, Katharina Kähler, Rudolf Stadler, Carola Berking, Christoph Höller, Laura Kerschke, Lutz Edler, Annette Kopp-Schneider, Jürgen C Becker
Chemotherapy still plays an important role in metastatic melanoma, particularly for patients who are not suitable or have no access to highly efficacious new therapies. Pre-therapeutic chemosensitivity testing might be useful to identify optimal chemotherapy regimens for individual patients. This multicenter randomized phase-3 trial was aimed to test for superiority of chemosensitivity-directed combination chemotherapy compared to standard dacarbazine monochemotherapy, and to demonstrate the chemosensitivity test result as prognostic in metastatic melanoma...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100193/phase-ii-multicentre-randomised-trial-of-eribulin-plus-gemcitabine-versus-paclitaxel-plus-gemcitabine-as-first-line-chemotherapy-in-patients-with-her2-negative-metastatic-breast-cancer
#13
Yeon Hee Park, Seock-Ah Im, Sung-Bae Kim, Joo Hyuk Sohn, Keun Seok Lee, Yee Soo Chae, Ki Hyeong Lee, Jee Hyun Kim, Young-Hyuck Im, Ji-Yeon Kim, Tae-Yong Kim, Kyung-Hun Lee, Jin-Hee Ahn, Gun Min Kim, In Hae Park, Soo Jung Lee, Hye Sook Han, Se Hyun Kim, Kyung Hae Jung
BACKGROUND: Paclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel. PATIENTS AND METHODS: This study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC...
November 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29096687/synergistic-effects-of-combining-proteasome-inhibitors-with-chemotherapeutic-drugs-in-lung-cancer-cells
#14
Linda Sooman, Joachim Gullbo, Michael Bergqvist, Stefan Bergström, Johan Lennartsson, Simon Ekman
BACKGROUND: The prognosis for patients with disseminated lung cancer is poor and current treatments have limited survival benefit as resistance often occurs, and is often associated with significant toxicity. A possible strategy to improve treatment and evade chemoresistance may be to find new combinations of drugs. The aim of this study was to analyze the potential of combining proteasome inhibitors (PIs) with chemotherapeutic drugs used in the routine treatment for lung cancer patients...
November 2, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29080971/combination-chemotherapy-with-irinotecan-and-gemcitabine-for-taxane-platinum-resistant-refractory-ovarian-and-primary-peritoneal-cancer-a-multicenter-phase-i-ii-trial-gogo-ov-6
#15
Kiyoshi Yoshino, Shoji Kamiura, Takeshi Yokoi, Ruriko Nakae, Masami Fujita, Masahiko Takemura, Kazushige Adachi, Akinori Wakimoto, Takamichi Nishizaki, Yasuhiko Shiki, Tateki Tsutsui, Yuki Kanda, Eiji Kobayashi, Kae Hashimoto, Seiji Mabuchi, Yutaka Ueda, Kenjiro Sawada, Takuji Tomimatsu, Tadashi Kimura
PURPOSE: To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy. METHODS: Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m(2), respectively; level 2: 100 and 1000 mg/m(2)) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity...
October 28, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29069637/redox-active-metals-and-h2o2-mediate-the-increased-efficacy-of-pharmacological-ascorbate-in-combination-with-gemcitabine-or-radiation-in-pre-clinical-sarcoma-models
#16
Joshua D Schoenfeld, Zita A Sibenaller, Kranti A Mapuskar, Megan D Bradley, Brett A Wagner, Garry R Buettner, Varun Monga, Mohammed Milhem, Douglas R Spitz, Bryan G Allen
Soft tissue sarcomas are a histologically heterogeneous group of rare mesenchymal cancers for which treatment options leading to increased overall survival have not improved in over two decades. The current study shows that pharmacological ascorbate (systemic high dose vitamin C achieving ≥ 20mM plasma levels) is a potentially efficacious and easily integrable addition to current standard of care treatment strategies in preclinical models of fibrosarcoma and liposarcoma both in vitro and in vivo. Furthermore, enhanced ascorbate-mediated toxicity and DNA damage in these sarcoma models were found to be dependent upon H2O2 and intracellular labile iron...
September 28, 2017: Redox Biology
https://www.readbyqxmd.com/read/29061832/neoadjuvant-chemotherapy-for-patients-with-muscle-invasive-urothelial-bladder-cancer-candidates-for-curative-surgery-a-prospective-clinical-trial-based-on-cisplatin-feasibility
#17
COMPARATIVE STUDY
Giovanni Schinzari, Santa Monterisi, Francesco Pierconti, Giulia Nazzicone, Laura Marandino, Armando Orlandi, Marco Racioppi, Alessandra Cassano, Pierfrancesco Bassi, Carlo Barone, Ernesto Rossi
BACKGROUND: Neoadjuvant chemotherapy demonstrated a survival benefit versus cystectomy alone in muscle-invasive urothelial bladder cancer. Despite this advantage, preoperative chemotherapy is not widely employed. When patients are unfit for cisplatin-based regimen, they are often candidates for immediate surgery. In our study, patients with muscle-invasive bladder cancer were treated with neoadjuvant chemotherapy. The principal objective was the rate of complete pathological response (pCR)...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29044544/primary-systemic-therapy-in-resectable-pancreatic-ductal-adenocarcinoma-using-mfolfirinox-a-pilot-study
#18
Robert de W Marsh, Mark S Talamonti, Marshall S Baker, Mitchell Posner, Kevin Roggin, Jeffrey Matthews, Daniel Catenacci, Mark Kozloff, Blase Polite, Michele Britto, Chi Wang, Hedy Kindler
BACKGROUND AND OBJECTIVES: Surgery followed by gemcitabine and/or a fluoropyrimidine is standard therapy for resectable PDAC. mFOLFIRINOX (oxaliplatin 85 mg/m(2) , irinotecan 180 mg/m(2) , leucovorin 400 mg/m(2) Day 1, 5-FU 2400 mg/m(2)  × 48 h IV, peg-filgrastim 6 mg SQ day 3, every 14 days) has substantial activity in metastatic PDAC. We wished to determine the tolerability/efficacy of peri-operative mFOLFIRINOX in resectable PDAC. METHODS: Patients with resectable PDAC (ECOG PS 0/1) received four cycles of mFOLFIRINOX pre- and post-surgery...
October 16, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29040974/an-intergroup-randomized-phase-ii-study-of-bevacizumab-or-cetuximab-in-combination-with-gemcitabine-and-in-combination-with-chemoradiation-in-patients-with-resected-pancreatic-carcinoma-a-trial-of-the-ecog-acrin-cancer-research-group-e2204
#19
Jordan D Berlin, Yang Feng, Paul Catalano, James L Abbruzzese, Philip A Philip, Robert R McWilliams, Andrew M Lowy, Al B Benson Iii, A William Blackstock
OBJECTIVES: Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS). METHODS: Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of cetuximab/bevacizumab...
October 18, 2017: Oncology
https://www.readbyqxmd.com/read/29038584/dual-drug-containing-core-shell-nanoparticles-for-lung-cancer-therapy
#20
Jyothi U Menon, Aneetta Kuriakose, Roshni Iyer, Elizabeth Hernandez, Leah Gandee, Shanrong Zhang, Masaya Takahashi, Zhang Zhang, Debabrata Saha, Kytai T Nguyen
Late-stage diagnosis of lung cancer occurs ~95% of the time due to late manifestation of its symptoms, necessitating rigorous treatment following diagnosis. Existing treatment methods are limited by lack of specificity, systemic toxicity, temporary remission, and radio-resistance in lung cancer cells. In this research, we have developed a folate receptor-targeting multifunctional dual drug-loaded nanoparticle (MDNP) containing a poly(N-isopropylacrylamide)-carboxymethyl chitosan shell and poly lactic-co-glycolic acid (PLGA) core for enhancing localized chemo-radiotherapy to effectively treat lung cancers...
October 16, 2017: Scientific Reports
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