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Gemcitabine toxicity

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https://www.readbyqxmd.com/read/28424962/phase-i-dose-escalation-study-of-milciclib-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#1
Sandrine Aspeslagh, Kunwar Shailubhai, Rastilav Bahleda, Anas Gazzah, Andréa Varga, Antoine Hollebecque, Christophe Massard, Anna Spreafico, Michele Reni, Jean-Charles Soria
BACKGROUND: This phase I trial evaluated the safety and tolerability of milciclib, an inhibitor of multiple cyclin-dependent kinases and tropomycin receptor kinase A, in combination with gemcitabine in patients with refractory solid tumors. DESIGN: Sixteen patients were enrolled and treated with milciclib at three dose levels (45 mg/m(2)/day, n = 3; 60 mg/m(2)/day, n = 3; and 80 mg/m(2)/day, n = 10) with a fixed dose of gemcitabine (1000 mg/m(2)/day). Milciclib was administered orally once daily for 7 days on/7 days off in a 4-week cycle, and gemcitabine was administered intravenously on days 1, 8 and 15 in a 4-week cycle...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28422841/evaluation-of-gemcitabine-efficacy-after-the-folfirinox-regimen-in-patients-with-advanced-pancreatic-adenocarcinoma
#2
Marine Gilabert, Brice Chanez, Young Soo Rho, Marc Giovanini, Olivier Turrini, Gerald Batist, Petr Kavan, Jean Luc Raoul
To evaluate gemcitabine efficacy in advanced pancreatic cancer patients after the FOLFIRINOX regimen.Patients with locally-advanced or metastatic pancreatic adenocarcinoma from French and Canadian centers, who were treated with the first-line FOLFIRINOX regimen (FFX L1), followed by gemcitabine monotherapy as a second-line treatment (GEM L2), were retrospectively evaluated. Statistical analyses were performed on the demographic, toxicity, and response rate data. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28399521/neoadjuvant-chemotherapy-with-gemcitabine-plus-cisplatin-in-patients-with-locally-advanced-bladder-cancer
#3
Dora Niedersüss-Beke, Thomas Puntus, Thomas Kunit, Birgit Grünberger, Michael Lamche, Wolfgang Loidl, Reinhard Böhm, Nicole Kraischits, Stefan Kudlacek, Paul Schramek, Johannes G Meran
BACKGROUND: Neoadjuvant chemotherapy with methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) is the standard of care for muscle-invasive urothelial bladder cancer. Gemcitabine plus cisplatin (GC) shows similar efficacy with less toxicity in the metastatic setting and has therefore often been used interchangeably with MVAC. We report on the efficacy and safety of neoadjuvant GC in patients with locally advanced urothelial cancer. MATERIALS AND METHODS: We prospectively evaluated 87 patients in 2 centers...
April 12, 2017: Oncology
https://www.readbyqxmd.com/read/28398845/potentially-curable-pancreatic-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#4
Alok A Khorana, Pamela B Mangu, Jordan Berlin, Anitra Engebretson, Theodore S Hong, Anirban Maitra, Supriya G Mohile, Matthew Mumber, Richard Schulick, Marc Shapiro, Susan Urba, Herbert J Zeh, Matthew H G Katz
Purpose To update the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline published on May 31, 2016. The October 2016 update focuses solely on new evidence that pertains to clinical question 4 of the guideline: What is the appropriate adjuvant regimen for patients with pancreatic cancer who have undergone an R0 or R1 resection of their primary tumor? Methods The recently published results of a randomized phase III study prompted an update of this guideline...
April 11, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28397697/nab-paclitaxel-plus-either-gemcitabine-or-simplified-leucovorin-and-fluorouracil-as-first-line-therapy-for-metastatic-pancreatic-adenocarcinoma-afugem-gercor-a-non-comparative-multicentre-open-label-randomised-phase-2-trial
#5
Jean-Baptiste Bachet, Pascal Hammel, Jérôme Desramé, Aurélia Meurisse, Benoist Chibaudel, Thierry André, Philippe Debourdeau, Jérome Dauba, Thierry Lecomte, Jean-François Seitz, Christophe Tournigand, Thomas Aparicio, Véronique Guerin Meyer, Julien Taieb, Julien Volet, Amandine Monier, Franck Bonnetain, Christophe Louvet
BACKGROUND: Nab-paclitaxel plus gemcitabine has become a standard treatment regimen in patients with metastatic pancreatic adenocarcinoma; however, retrospective data suggest that gemcitabine might be inefficient in 50-60% of patients and thus not an optimum regimen in combination with nab-paclitaxel. We did a phase 2 trial to assess the activity and safety of a new regimen of nab-paclitaxel plus simplified leucovorin and fluorouracil. METHODS: We did a non-comparative, multicentre, open-label, randomised phase 2 trial in 15 hospitals and institutions in France...
May 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28397047/efficacy-and-safety-of-chemotherapy-with-or-without-targeted-therapy-in-biliary-tract-cancer-a-meta-analysis-of-7-randomized-controlled-trials
#6
Xin Zhuang, Ya-Ping Xiao, Ling-Hua Tan, Lu-Ting Wang, Qian Cao, Gui-Fang Qu, Shuang Xiao, Hua-Xin Duan
The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers. However, the exact benefits from the recognized regime are still dismal. We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits. The clinical trials were searched electronically from databases till July 2016 published in English and Chinese. Nine hundred and sixty-four patients from 7 trials were identified in our analysis...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28396636/enhancing-drug-efficacy-and-therapeutic-index-through-cheminformatics-based-selection-of-small-molecule-binary-weapons-that-improve-transporter-mediated-targeting-a-cytotoxicity-system-based-on-gemcitabine
#7
Justine M Grixti, Steve O'Hagan, Philip J Day, Douglas B Kell
The transport of drug molecules is mainly determined by the distribution of influx and efflux transporters for which they are substrates. To enable tissue targeting, we sought to develop the idea that we might affect the transporter-mediated disposition of small-molecule drugs via the addition of a second small molecule that of itself had no inhibitory pharmacological effect but that influenced the expression of transporters for the primary drug. We refer to this as a "binary weapon" strategy. The experimental system tested the ability of a molecule that on its own had no cytotoxic effect to increase the toxicity of the nucleoside analog gemcitabine to Panc1 pancreatic cancer cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28391352/the-impact-of-a-solitary-kidney-on-tolerability-to-gemcitabine-plus-cisplatin-chemotherapy-in-urothelial-carcinoma-patients-a-retrospective-study
#8
Masahiro Kondo, Yuji Hotta, Ryosuke Ando, Takahiro Yasui, Kazunori Kimura
PURPOSE: There is little information on tolerability to cisplatin-based chemotherapies in patients with a solitary kidney after nephroureterectomy. We evaluated the impact of having a solitary kidney on tolerability to gemcitabine plus cisplatin (GC) chemotherapy in urothelial carcinoma patients. METHODS: We retrospectively reviewed medical records of patients treated between August 2007 and November 2015. Eligible patients had received GC as first-line chemotherapy, including as neoadjuvant and adjuvant treatment...
April 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28389316/maintenance-therapy-with-vinflunine-plus-best-supportive-care-versus-best-supportive-care-alone-in-patients-with-advanced-urothelial-carcinoma-with-a-response-after-first-line-chemotherapy-maja-sogug-2011-02-a-multicentre-randomised-controlled-open-label-phase
#9
Jesus García-Donas, Albert Font, Begoña Pérez-Valderrama, José Antonio Virizuela, Miquel Ángel Climent, Susana Hernando-Polo, José Ángel Arranz, Maria Del Mar Llorente, Nuria Lainez, José Carlos Villa-Guzmán, Begoña Mellado, Aránzazu González Del Alba, Daniel Castellano, Enrique Gallardo, Urbano Anido, Xavier García Del Muro, Montserrat Domènech, Javier Puente, Rafael Morales-Barrera, Jose Luis Pérez-Gracia, Joaquim Bellmunt
BACKGROUND: Maintenance therapy improves outcomes in various tumour types, but cumulative toxic effects limit the choice of drugs. We investigated whether maintenance therapy with vinflunine would delay disease progression in patients with advanced urothelial carcinoma who had achieved disease control with first-line chemotherapy. METHODS: We did a randomised, controlled, open-label, phase 2 trial in 21 Spanish hospitals. Eligible patients had locally advanced, surgically unresectable, or metastatic transitional-cell carcinoma of the urothelial tract, adequate organ function, and disease control after four to six cycles of cisplatin and gemcitabine (carboplatin allowed after cycle four)...
April 4, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28379023/-cardiovascular-complications-of-cancers-and-anti-cancer-therapy
#10
Jiří Vyskočil, Katarína Petráková, Petr Jelínek, Michal Furdek
In our aging population the incidence of cancer is increasing in the elderly. We are thus facing a new challenge especially considering incidence of cardiovascular diseases (CVD) in this patients population. Overall survival of cancer patients has significantly improved therefore cancer has become in many cases a chronic disease. We are about to be treating patients who either may develop a new CVD or their current CVD may deteriorate. Cancer can cause various cardiovascular conditions locally (pressure in mediastinum, effusions) or systemically (increased risk of pulmonary embolism, arrhythmias, carcinoid heart disease)...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28378027/a-phase-ii-trial-of-neoadjuvant-chemoradiotherapy-with-intensity-modulated-radiotherapy-combined-with-gemcitabine-and-s-1-for-borderline-resectable-pancreatic-cancer-with-arterial-involvement
#11
Yuichi Nagakawa, Yuichi Hosokawa, Hidetsugu Nakayama, Yatsuka Sahara, Chie Takishita, Tetsushi Nakajima, Yousuke Hijikata, Kazuhiko Kasuya, Kenji Katsumata, Koichi Tokuuye, Akihiko Tsuchida
PURPOSE: Chemoradiotherapy using intensity-modulated radiotherapy (IMRT) is expected to provide a powerful alternative to conventional chemotherapy with a low incidence of adverse events. This study evaluated the efficacy of intensity modulated radiotherapy in combination with gemcitabine and S-1 as neoadjuvant chemoradiotherapy (NACRT) for borderline-resectable pancreatic cancer with arterial involvement (BR-A). METHODS: A total of 27 patients with BR-A were enrolled in this study between February 2012 and September 2015...
April 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28373469/nab-paclitaxel-and-gemcitabine-in-advanced-pancreatic-cancer-the-one-year-experience-of-the-national-cancer-institute-of-naples
#12
Alessandro Ottaiano, Monica Capozzi, Chiara DE Divitiis, Claudia VON Arx, Elena DI Girolamo, Guglielmo Nasti, Ernesta Cavalcanti, Fabiana Tatangelo, Giovanni Romano, Antonio Avallone, Salvatore Tafuto
BACKGROUND: Pancreas adenocarcinoma is the sixth cause of cancer-related death worldwide with an increasing mortality in the Western countries. Recently, the association between nab-paclitaxel (nab-P) and gemcitabine (GEM) has significantly improved progression-free and overall survival. PATIENTS AND METHODS: Patients affected by metastatic pancreas adenocarcinoma were treated at the Department of Abdominal Oncology of the National Cancer Institute of Naples from July 2015 to July 2016 with nab-P at 125 mg per square meter of body-surface area followed by GEM at 1,000 mg per square meter on days 1, 8 and 15 every 4 weeks...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28366930/gemcitabine-conjugated-chitosan-and-double-antibodies-abc-gc-gemcitabine-nanoparticles-enhanced-cytoplasmic-uptake-of-gemcitabine-and-inhibit-proliferation-and-metastasis-in-human-sw1990-pancreatic-cancer-cells
#13
Jun Xiao, Haibo Yu
BACKGROUND Pancreatic cancer is considered a chemoresistant neoplasm with extremely dismal prognosis and gemcitabine treatment is associated with many side effects and poor overall survival. The study aimed at developing a new nanobioconjugate, which specifically delivered gemcitabine and anti-EGFR antibody into pancreatic cancer cells. MATERIAL AND METHODS The novel nanodrug is based on chitosan platform, which is non-toxic, biocompatibility and biodegradable. We measured the effects of proliferation and metastasis on SW1990 by CCK-8 assay, colony formation assay, wound healing assay and Transwell assay...
April 3, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28365238/an-open-label-randomized-controlled-phase-ii-study-of-paclitaxel-carboplatin-chemotherapy-with-necitumumab-versus-paclitaxel-carboplatin-alone-in-first-line-treatment-of-patients-with-stage-iv-squamous-non-small-cell-lung-cancer
#14
David R Spigel, Alexander Luft, Henrik Depenbrock, Rodryg Ramlau, Mazen Khalil, Joo-Hang Kim, Carlos Mayo, Grace Yi Chao, Coleman Obasaju, Ronald Natale
BACKGROUND: The combination of necitumumab with gemcitabine-cisplatin significantly improved overall survival (OS) in patients with stage IV squamous non-small-cell lung cancer (NSCLC), in the phase III SQUamous NSCLC treatment with the Inhibitor of EGF REceptor (SQUIRE) trial. Paclitaxel-carboplatin was selected as an alternative standard of care in the current phase II study. PATIENTS AND METHODS: Patients were randomized (stratified according to Eastern Cooperative Oncology Group performance status and sex) 2:1 to ≤ six 3-week cycles (Q3W) of paclitaxel and carboplatin with or without necitumumab...
March 2, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28365185/curcumin-and-its-cyclohexanone-analogue-inhibited-human-equilibrative-nucleoside-transporter-1-ent1-in-pancreatic-cancer-cells
#15
Jezrael L Revalde, Yan Li, Tharaka S Wijeratne, Piyush Bugde, Bill C Hawkins, Rhonda J Rosengren, James W Paxton
Our group investigated combining the phytochemical curcumin and gemcitabine in a liposome, to improve gemcitabine's activity against pancreatic tumours. While optimising the curcumin: gemcitabine ratio for co-encapsulation, we found that increasing curcumin concentrations relative to gemcitabine resulted in antagonistic interactions. As curcumin is a promiscuous transporter inhibitor; we suspected that increased resistance occurred via inhibition of Equilibrative nucleoside transporter 1 (ENT1)-mediated gemcitabine uptake...
March 29, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28361521/gemcitabine-and-docetaxel-combination-for-advanced-soft-tissue-sarcoma-a-nationwide-retrospective-study
#16
Yunjung Choi, Mi Sun Yun, Sang Hee Lim, Jeeyun Lee, Jin-Hee Ahn, Yu Jung Kim, Kyong Hwa Park, Young Suk Park, Ho Yeong Lim, Hyonggin An, Dong-Churl Suh, Yeul Hong Kim
Purpose: This nationwide retrospective study was conducted to evaluate the efficacy and safety of combined gemcitabine and docetaxel (GD) as an off-label therapy for advanced soft tissue sarcoma, which has limited treatment options owing to its rare occurrence. Materials and Methods: A total of 228 patients received GD therapy for advanced soft tissue sarcoma from 2009 to 2014 in Korea. We retrospectively reviewed the clinical medical records and claims data of these patients...
March 30, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28353074/gemcitabine-in-combination-with-a-second-cytotoxic-agent-in-the-first-line-treatment-of-locally-advanced-or-metastatic-pancreatic-cancer-a-systematic-review-and-meta-analysis
#17
REVIEW
Xiu-Wei Zhang, Yu-Xiang Ma, Yang Sun, Yu-Bo Cao, Qin Li, Chong-An Xu
BACKGROUND: It remains controversial whether the addition of a second cytotoxic agent can further improve the therapeutic effect of gemcitabine monotherapy in advanced or metastatic pancreatic cancer (LA/MPC). OBJECTIVE: The objective of the present systematic review and meta-analysis was to investigate the efficacy and safety of gemcitabine-based doublet chemotherapy regimens compared to single-agent gemcitabine in the first-line treatment of unresectable LA/MPC...
March 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28350787/quality-adjusted-survival-with-combination-nal-iri-5-fu-lv-vs-5-fu-lv-alone-in-metastatic-pancreatic-cancer-patients-previously-treated-with-gemcitabine-based-therapy-a-q-twist-analysis
#18
Uwe Pelzer, Jean-Frédéric Blanc, Davide Melisi, Antonio Cubillo, Daniel D Von Hoff, Andrea Wang-Gillam, Li-Tzong Chen, Jens T Siveke, Yin Wan, Caitlyn T Solem, Marc F Botteman, Yoojung Yang, Floris A de Jong, Richard A Hubner
BACKGROUND: In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). METHODS: Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST)...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28348976/combination-of-photon-and-carbon-ion-irradiation-with-targeted-therapy-substances-temsirolimus-and-gemcitabine-in-hepatocellular-carcinoma-cell-lines
#19
Sarah Dehne, Clarissa Fritz, Stefan Rieken, Daniela Baris, Stephan Brons, Thomas Haberer, Jürgen Debus, Klaus-Josef Weber, Thomas E Schmid, Stephanie E Combs, Daniel Habermehl
BACKGROUND: This work investigates on putative cytotoxic effects in four different hepatocellular carcinoma (HCC) cell lines after irradiation with photons or carbon ions in combination with new targeted molecular therapy using either Temsirolimus (TEM) or Gemcitabine (GEM). METHODS AND MATERIALS: The HCC cell lines HepG2, Hep3B, HuH7, and PLC were cultured and irradiated with photons or carbon ions at the Heidelberg Ion Beam Therapy Center using the raster-scanning method...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28346313/population-pharmacokinetics-of-gemcitabine-and-dfdu-in-pancreatic-cancer-patients-using-an-optimal-design-sparse-sampling-approach
#20
Cindy Serdjebi, Florence Gattacceca, Jean-François Seitz, Francine Fein, Johan Gagnière, Eric François, Abakar Abakar-Mahamat, Gael Deplanque, Madani Rachid, Bruno Lacarelle, Joseph Ciccolini, Laetitia Dahan
BACKGROUND: Gemcitabine remains a pillar in pancreatic cancer treatment. However, toxicities are frequently observed. Dose adjustment based on therapeutic drug monitoring might help decrease the occurrence of toxicities. In this context, this work aims at describing the pharmacokinetics (PK) of gemcitabine and its metabolite dFdU in pancreatic cancer patients and at identifying the main sources of their PK variability using a population pharmacokinetics approach, despite a sparse sampled-population and heterogeneous administration and sampling protocols...
March 24, 2017: Therapeutic Drug Monitoring
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