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Gemcitabine toxicity

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https://www.readbyqxmd.com/read/29775835/analysis-of-the-cytotoxic-effects-of-combined-ultrasound-microbubble-and-nucleoside-analog-combinations-on-pancreatic-cells-in-vitro
#1
Julia Mariglia, Shadab Momin, Imogen R Coe, Raffi Karshafian
Ultrasonically-stimulated microbubbles enhance the therapeutic effects of various chemotherapy drugs. However, the application of ultrasound and microbubbles (USMB) for enhancing the therapeutic effect of nucleoside analogs, which are used as front-line treatments in a range of cancers, and its underlying mechanism is not well understood. This study investigated the effect of gemcitabine, a nucleoside analog drug, in combination with USMB in increasing cell cytotoxicity relative to either treatment alone in BxPC3 pancreatic cancer cells...
May 5, 2018: Ultrasonics
https://www.readbyqxmd.com/read/29770997/gemcitabine-nab-paclitaxel-for-pediatric-relapsed-refractory-sarcomas
#2
Jonathan L Metts, Adina L Alazraki, Dana Clark, Ernest K Amankwah, Karen J Wasilewski-Masker, Bradley A George, Thomas A Olson, Thomas Cash
BACKGROUND: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. PROCEDURE: We reviewed the records of fifteen relapsed/refractory patients and one treatment-naïve patient who received gemcitabine/nab-paclitaxel at our institution...
May 17, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29768050/getting-up-to-date-in-the-management-of-soft-tissue-sarcoma
#3
Jean-Yves Blay
Surgery (+ radiation therapy in selected cases) is standard treatment for adult-type localized soft tissue sarcoma (STS). Accumulating randomized clinical evidence also supports adjuvant chemotherapy as a treatment option, although this remains contentious. Doxorubicin (± ifosfamide) is the standard first-line systemic treatment for advanced STS; however, newer chemotherapeutic agents may improve outcomes achieved with single-agent doxorubicin. In a Phase II study, adding olaratumab to doxorubicin markedly improved overall survival...
May 2018: Future Oncology
https://www.readbyqxmd.com/read/29753120/a-phase-i-trial-of-surgical-resection-and-intraoperative-hyperthermic-cisplatin-and-gemcitabine-for-pleural-mesothelioma
#4
Bryan M Burt, William G Richards, Hyun-Sung Lee, Sylvia Bartel, Marcelo C Dasilva, Ritu R Gill, Michael T Jaklitsch, Bruce E Johnson, Scott J Swanson, Raphael Bueno, David J Sugarbaker
INTRODUCTION: The primary objective of this single-institution Phase I clinical trial was to establish the maximum tolerated dose (MTD) of gemcitabine added to cisplatin delivered as heated intraoperative chemotherapy (HIOC) following resection of malignant pleural mesothelioma (MPM). METHODS: Extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) treatment arms were based on investigators' assessment of patient fitness and potential for macroscopic complete resection...
May 9, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29752199/gemcitabine-oxaliplatin-plus-rituximab-r-gemox-as-first-line-treatment-in-elderly-patients-with-diffuse-large-b-cell-lymphoma-a-single-arm-open-label-phase-2-trial
#5
Qiu-Dan Shen, Hua-Yuan Zhu, Li Wang, Lei Fan, Jin-Hua Liang, Lei Cao, Wei Wu, Yi Xia, Jian-Yong Li, Wei Xu
BACKGROUND: The combination of rituximab, gemcitabine, and oxaliplatin (R-GemOx) has shown high efficacy with a low toxicity profile in elderly patients with relapsed and refractory diffuse large B-cell lymphoma. We aimed to evaluate the efficacy, safety, and feasibility of the R-GemOx regimen as a first-line treatment in elderly patients with diffuse large B-cell lymphoma. METHODS: In this single-arm, open-label, phase 2 clinical trial, we enrolled patients with previously untreated, histologically confirmed, CD20-positive diffuse large B-cell lymphoma, aged 70 years or older, or aged 60-69 years with an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or greater...
May 8, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29751792/discovering-novel-snps-that-are-correlated-with-patient-outcome-in-a-singaporean-cancer-patient-cohort-treated-with-gemcitabine-based-chemotherapy
#6
Vachiranee Limviphuvadh, Chee Seng Tan, Fumikazu Konishi, Piroon Jenjaroenpun, Joy Shengnan Xiang, Yuliya Kremenska, Yar Soe Mu, Nicholas Syn, Soo Chin Lee, Ross A Soo, Frank Eisenhaber, Sebastian Maurer-Stroh, Wei Peng Yong
BACKGROUND: Single Nucleotide Polymorphisms (SNPs) can influence patient outcome such as drug response and toxicity after drug intervention. The purpose of this study is to develop a systematic pathway approach to accurately and efficiently predict novel non-synonymous SNPs (nsSNPs) that could be causative to gemcitabine-based chemotherapy treatment outcome in Singaporean non-small cell lung cancer (NSCLC) patients. METHODS: Using a pathway approach that incorporates comprehensive protein-protein interaction data to systematically extend the gemcitabine pharmacologic pathway, we identified 77 related nsSNPs, common in the Singaporean population...
May 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29750040/a-phase-ib-study-of-ruxolitinib-gemcitabine-%C3%A2-nab-paclitaxel-in-patients-with-advanced-solid-tumors
#7
Todd M Bauer, Manish R Patel, Andres Forero-Torres, Thomas J George, Albert Assad, Yining Du, Herbert Hurwitz
Purpose: Aberrant activation of the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is associated with increased malignant cell proliferation and survival. This Phase Ib study evaluated ruxolitinib, a potent JAK1/2 inhibitor, in combination with gemcitabine with or without nab-paclitaxel in patients with advanced solid tumors. Patients and methods: Patients received ruxolitinib + gemcitabine (regimen A) or ruxolitinib + gemcitabine + nab-paclitaxel (regimen B)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29748012/a-phase-i-study-of-nintedanib-combined-with-cisplatin-gemcitabine-as-first-line-therapy-for-advanced-squamous-non-small-cell-lung-cancer-lume-lung-3
#8
Martin Forster, Allan Hackshaw, Tommaso De Pas, Manuel Cobo, Pilar Garrido, Yvonne Summers, Anne-Marie C Dingemans, Michael Flynn, David Schnell, Ute von Wangenheim, Arsene-Bienvenu Loembé, Rolf Kaiser, Siow Ming Lee
BACKGROUND: There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. MATERIALS AND METHODS: A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2 , Day 1), gemcitabine (1250 mg/m2 , Days 1 and 8) and nintedanib (Days 2-7, 9-21) were given for 4-6 cycles, followed by monotherapy until disease progression or adverse events (AEs)...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29745095/phase-i-study-of-gemcitabine-cisplatin-versus-pemetrexed-cisplatin-for-patients-with-advanced-or-metastatic-bladder-cancer
#9
Yifang Cao, Yi He, Hao Chen, Shunliang He, Yanqin Gu, Xueping Wang, Bin Chen
PURPOSE: The present study aimed to compare the chemotherapeutic regimens of gemcitabine plus cisplatin (GC) vs pemetrexed plus cisplatin (PC) in bladder cancer (BC) with vascular invasion and/or distant metastasis. METHODS: From January 2010 to January 2017, 53 patients with advanced or metastatic BC were included and randomly divided into two groups. Patients in the GC group were administered 1,000 mg/m2 gemcitabine on day 1 and 15 and 70 mg/m2 cisplatin on day 1 as an IV infusion...
March 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29742194/widespread-skin-necrosis-secondary-to-gemcitabine-therapy
#10
Patrick M Zito, Adrianna M Gonzalez, Joshua D Fox, Megan Cronin, Nicholas Mackrides, Robert S Kirsner, Anna J Nichols
Gemcitabine, a pyrimidine nucleoside analogue, is an oncologic agent used in the treatment of cutaneous T-cell lymphoma (CTCL). Common dermatologic reactions associated with gemcitabine include alopecia, mild skin rash, and mucositis but skin necrosis is exceptional. Herein we present an unusual case of widespread skin necrosis mimicking toxic epidermal necrolysis in a 45-year-old woman receiving gemcitabine therapy for stage IIIA cutaneous T-cell lymphoma. This is the first reported case of a TEN-like reaction subsequent to gemcitabine treatment...
May 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29742009/multicenter-prospective-phase-ii-trial-of-neoadjuvant-dose-dense-gemcitabine-plus-cisplatin-in-patients-with-muscle-invasive-bladder-cancer
#11
Gopa Iyer, Arjun V Balar, Matthew I Milowsky, Bernard H Bochner, Guido Dalbagni, S Machele Donat, Harry W Herr, William C Huang, Samir S Taneja, Michael Woods, Irina Ostrovnaya, Hikmat Al-Ahmadie, Maria E Arcila, Jamie C Riches, Andreas Meier, Caitlin Bourque, Maha Shady, Helen Won, Tracy L Rose, William Y Kim, Brooke E Kania, Mariel E Boyd, Catharine K Cipolla, Ashley M Regazzi, Daniela Delbeau, Asia S McCoy, Hebert Alberto Vargas, Michael F Berger, David B Solit, Jonathan E Rosenberg, Dean F Bajorin
Purpose Neoadjuvant chemotherapy followed by radical cystectomy (RC) is a standard of care for the management of muscle-invasive bladder cancer (MIBC). Dose-dense cisplatin-based regimens have yielded favorable outcomes compared with standard-dose chemotherapy, yet the optimal neoadjuvant regimen remains undefined. We assessed the efficacy and tolerability of six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with MIBC. Patients and Methods In this prospective, multicenter phase II study, patients received ddGC (gemcitabine 2,500 mg/m2 on day 1 and cisplatin 35 mg/m2 on days 1 and 2) every 2 weeks for 6 cycles followed by RC...
May 9, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29740790/identification-of-inhibitors-synergizing-gemcitabine-sensitivity-in-the-squamous-subtype-of-pancreatic-ductal-adenocarcinoma-pdac
#12
Jia Lin Er, Pei Ni Goh, Chen Yuan Lee, Ying Jie Tan, Ling-Wei Hii, Chun Wai Mai, Felicia Fei-Lei Chung, Chee-Onn Leong
Pancreatic adenocarcinoma (PDAC) is a highly aggressive cancer with a high chance of recurrence, limited treatment options, and poor prognosis. A recent study has classified pancreatic cancers into four molecular subtypes: (1) squamous, (2) immunogenic, (3) pancreatic progenitor and (4) aberrantly differentiated endocrine exocrine. Among all the subtypes, the squamous subtype has the worst prognosis. This study aims to utilize large scale genomic datasets and computational systems biology to identify potential drugs targeting the squamous subtype of PDAC through combination therapy...
May 8, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29735549/mechanistic-distinctions-between-chk1-and-wee1-inhibition-guide-the-scheduling-of-triple-therapy-with-gemcitabine
#13
Siang-Boon Koh, Yann Wallez, Charles R Dunlop, Sandra Bernaldo de Quirós Fernández, Tashinga E Bapiro, Frances M Richards, Duncan I Jodrell
Combination of cytotoxic therapy with emerging DNA damage response inhibitors (DDRi) has been limited by tolerability issues. However, the goal of most combination trials has been to administer DDRi with standard-of-care doses of chemotherapy. We hypothesised that mechanism-guided treatment scheduling could reduce the incidence of dose-limiting toxicities and enable tolerable multitherapeutic regimens. Integrative analyses of mathematical modelling and single-cell assays distinguished the synergy kinetics of WEE1i from CHK1i by potency, spatiotemporal perturbation, and mitotic effects when combined with gemcitabine...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29719589/combination-of-interferon-expressing-oncolytic-adenovirus-with-chemotherapy-and-radiation-is-highly-synergistic-in-hamster-model-of-pancreatic-cancer
#14
Amanda O Salzwedel, Joohee Han, Christopher J LaRocca, Ryan Shanley, Masato Yamamoto, Julia Davydova
Recent clinical trials utilizing Interferon-alpha (IFN) in combination with chemoradiation have demonstrated significant improvements in the survival of patients with pancreatic cancer. However, efficacy was limited by the systemic toxicity of IFN and low intratumoral levels of the cytokine. We sought to address these drawbacks by using an Oncolytic Adenovirus expressing IFN (OAd-hamIFN) in combination with chemotherapy and/or radiation in regimens mimicking the IFN-based therapies used in clinical trials. IFN expressed from OAd-hamIFN potentiated the cytotoxicity of radiation and chemotherapy (5-FU, Gemcitabine, and Cisplatin), and enhanced pancreatic cancer cell death in both in vitro and in vivo experimental settings...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719014/mycosis-fungoides-clinical-and-histopathologic-features-differential-diagnosis-and-treatment
#15
Lorenzo Cerroni
Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. MF is divided into 3 clinical phases: patch, plaque, and tumor stage, and the clinical course is usually protracted over years or decades. Histopathologically, MF is characterized by an epidermotropic infiltrate of T lymphocytes that displays in most cases a helper phenotype...
March 2018: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/29718363/efficacy-and-safety-comparison-of-nabpaclitaxel-plus-s-1-and-gemcitabine-plus-s-1-as-first-line-chemotherapy-for-metastatic-pancreatic-cancer
#16
Yaolin Xu, Xi Guo, Yue Fan, Dansong Wang, Wenchuan Wu, Lili Wu, Tianshu Liu, Bei Xu, Yi Feng, Yan Wang, Wenhui Lou, Yuhong Zhou
Objective: To compare efficacy and safety of nabpaclitaxel plus S-1 (AS) with gemcitabine plus S-1 (GS) as first-line treatment for metastatic pancreatic cancer. Methods: We conducted a retrospective cohort, single-institution analysis by reviewing medical records of 38 patients who received either AS (nabpaclitaxel 125 mg/m2 on Days 1, 8 and S-1 80 mg/m2 on Days 1 to 14) or GS (gemcitabine 1000 mg/m2 on Days 1, 8 and S-1 80 mg/m2 on Days 1 to 14) chemotherapy. Results: AS was associated with a prolonged median time to progression (TTP; 7...
April 28, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29704518/inhibition-of-mapkapk2-mk2-facilitates-dna-replication-upon-cancer-cell-treatment-with-gemcitabine-but-not-cisplatin
#17
Yizhu Li, Frederik Köpper, Matthias Dobbelstein
The signaling pathway driven by p38 and MAPKAPK2 alias MK2 is activated as part of stress responses, and these kinases represent attractive drug targets for cancer therapy. However, seemingly conflicting results were obtained when assessing the role of MK2 in chemotherapy. MK2 inhibitors were reported to either enhance or diminish the chemosensitivity of cancer cells. Here we show that this strongly depends on the particular chemotherapeutic drug. Two different MK2 inhibitors increased the proliferating fraction of pancreatic cancer-derived cells upon treatment with gemcitabine, whereas no consistent protection against cisplatin was observed...
April 25, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29696360/randomized-phase-2-study-of-gemcitabine-and-cisplatin-with-or-without-vitamin-supplementation-in-patients-with-advanced-esophagogastric-cancer
#18
A A van Zweeden, C J van Groeningen, R J Honeywell, E Giovannetti, R Ruijter, C H Smorenburg, G Giaccone, H M W Verheul, G J Peters, Hans J van der Vliet
PURPOSE: Preclinical research and prior clinical observations demonstrated reduced toxicity and suggested enhanced efficacy of cisplatin due to folic acid and vitamin B12 suppletion. In this randomized phase 2 trial, we evaluated the addition of folic acid and vitamin B12 to first-line palliative cisplatin and gemcitabine in patients with advanced esophagogastric cancer (AEGC). METHODS: Patients with AEGC were randomized to gemcitabine 1250 mg/m2 (i.v. days 1, 8) and cisplatin 80 mg/m2 (i...
April 25, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29695765/phase-i-study-of-nab-paclitaxel-gemcitabine-and-bevacizumab-in-patients-with-advanced-cancers
#19
Shiraj Sen, Shumei Kato, Rishi Agarwal, Sarina Piha-Paul, Kenneth Hess, Daniel Karp, Filip Janku, Siqing Fu, Aung Naing, Shubham Pant, Gerald Falchook, Chad Tang, Xifeng Wu, Yuanqing Ye, Apostolia Tsimberidou, Vivek Subbiah, Razelle Kurzrock, Lauren Byers, Shannon Westin, JoAnn Lim, Stacie Bean, Allison Bass, Ly Nguyen, Funda Meric-Bernstam, David Hong
BACKGROUND: We performed a phase I modified 3 + 3 dose escalation study to evaluate the safety and activity of bevacizumab plus gemcitabine and nab-paclitaxel in patients with advanced solid tumours. METHODS: Patients were given fixed dose gemcitabine plus increasing doses of nab-paclitaxel and bevacizumab. Toxicity, response, and association with VEGF polymorphism was analysed. RESULTS: The study enrolled 110 patients who had undergone a median of 3 prior lines of therapy...
April 26, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29687847/clinical-effectiveness-of-pemetrexed-combined-with-cisplatin-chemotherapy-for-advanced-and-maintenance-treatment-for-patients-with-non-small-cell-lung-cancer
#20
Y-M Zhu, Y-L Gan, H-Y Xu, W-H Chen, H-P Dai
OBJECTIVE: To evaluate the clinical effectiveness of pemetrexed combined with cisplatin for the first-line chemotherapy of patients with advanced non-small-cell lung cancer (NSCLC) and maintenance treatment. PATIENTS AND METHODS: 240 advanced NSCLC patients were randomly divided into either a control group (treated with gemcitabine combined with cisplatin) or an observation group (treated with pemetrexed combined with cisplatin). The primary treatment was defined as first-line chemotherapy, and the maintenance treatment was defined as retreatment...
April 2018: European Review for Medical and Pharmacological Sciences
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