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Pemetrexed

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https://www.readbyqxmd.com/read/28915906/unusually-prolonged-pemetrexed-cytotoxicity-in-a-patient-with-a-lung-adenocarcinoma-a-case-report
#1
Linda Sakhri, Julian Pinsolle, Denis Moro-Sibilot, Hélène Pluchart
BACKGROUND: We describe a case of pemetrexed toxicities related to reabsorption by an ileal neobladder, which caused prolonged hematotoxicity and nephrotoxicity. CASE PRESENTATION: A 59-year-old white man was diagnosed with metastatic wild-type adenocarcinoma of the upper lobe of his right lung. After a first cycle of cisplatin and pemetrexed, he had unusually prolonged aplasia and acute kidney injury. The prolonged aplasia was caused by pemetrexed reabsorption by the ileal mucosa of the neobladder as pemetrexed was eliminated renally in an active form and is partly lipophilic...
September 16, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28915721/dramatic-response-of-ctnnb1-and-vegfr-2-mutant-temporal-bone-squamous-cell-carcinoma-to-bevacizumab-in-combination-with-pemetrexed
#2
Lai Wei, Lizhi Wang, Ziye Liu, Meiyi Wang, Weili Lu, Dewei Zhao, Bin Yang, Xuejun Kong, Yan Ding, Zhiqiang Wang
High recurrence rates and poor survival rates for late stage/advanced temporal bone squamous cell carcinoma with the standard treatments continues to be a significant challenge to otolaryngologists. Targeted therapy for temporal bone squamous cell carcinoma after relapse has not been reported. Here we present a 58-year-old man who was diagnosed with recurrent temporal bone squamous cell carcinoma and treated with a regimen developed using whole exome sequencing. Somatic mutations in genes encoding catenin beta 1 and vascular endothelial growth factor receptor 2 were identified in the patient's tumor sample compared to the normal tissue...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911085/a-randomized-open-label-multicenter-phase-3-study-to-compare-the-efficacy-and-safety-of-eribulin-to-treatment-of-physician-s-choice-in-patients-with-advanced-non-small-cell-lung-cancer
#3
N Katakami, E Felip, D R Spigel, J-H Kim, M Olivo, M Guo, H Nokihara, J C-H Yang, N Iannotti, M Satouchi, F Barlesi
Background: Eribulin is a microtubule dynamics inhibitor with a novel mechanism of action. This phase 3 study aimed to compare overall survival (OS) in patients with heavily pretreated non-small cell lung cancer (NSCLC) receiving eribulin to treatment of physician's choice (TPC). Patients and methods: Patients with advanced NSCLC who had received ≥2 prior therapies, including platinum-based doublet and epidermal growth factor receptor tyrosine kinase inhibitor, were randomly assigned to receive eribulin or TPC (gemcitabine, pemetrexed, vinorelbine, docetaxel)...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28901493/high-pemetrexed-sensitivity-of-docetaxel-resistant-a549-cells-is-mediated-by-tp53-status-and-downregulated-thymidylate-synthase
#4
Wei-Ting Kuo, Dom-Gene Tu, Ling-Yen Chiu, Gwo-Tarng Sheu, Ming-Fang Wu
The chemoresistance of non-small cell lung cancer (NSCLC) that occurs in docetaxel (DOC) chemotherapy substantially decreases the survival of patients. To overcome DOC-induced chemoresistance, we established DOC-selected A549 lung cancer sublines (A549/D16 and A549/D32) and revealed that both sublines were cross-resistant to vincristine (VCR) and doxorubicin (DXR). Notably, both sublines were more sensitive to pemetrexed (PEM) than parental cells according to MTT and clonogenic assays. The expression levels of thymidylate synthase (TS) and γ-glutamyl hydrolase (GGH) were downregulated in DOC-resistant sublines...
September 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28892431/nintedanib-plus-pemetrexed-cisplatin-in-patients-with-malignant-pleural-mesothelioma-phase-ii-results-from-the-randomized-placebo-controlled-lume-meso-trial
#5
Federica Grosso, Nicola Steele, Silvia Novello, Anna K Nowak, Sanjay Popat, Laurent Greillier, Thomas John, Natasha B Leighl, Martin Reck, Paul Taylor, David Planchard, Jens Benn Sørensen, Mark A Socinski, Ute von Wangenheim, Arsène Bienvenu Loembé, José Barrueco, Nassim Morsli, Giorgio Scagliotti
Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression...
September 11, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28885847/regulation-of-reduced-folate-carrier-rfc-by-vitamin-d-receptor-at-the-blood-brain-barrier
#6
Camille Alam, Md Tozammel Hoque, Richard H Finnell, I David Goldman, Reina Bendayan
Folates are essential for brain development and function. Folate transport in mammalian tissues is mediated by three major folate transport systems, i.e., reduced folate carrier (RFC), proton-coupled folate transporter (PCFT) and folate receptor alpha (FRα), known to be regulated by ligand-activated nuclear receptors such as vitamin D receptor (VDR). Folate uptake at the choroid plexus, which requires the actions of both FRα and PCFT, is critical to cerebral folate delivery. Inactivating FRα or PCFT mutations cause severe cerebral folate deficiency resulting in early childhood neurodegeneration...
September 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28885340/a-case-report-of-lung-adenocarcinoma-with-polyserous-effusions-as-the-onset-symptom
#7
Ping Han, Ruipin Yao, Dongxia Zhai, Chao Cheng, Fangyong Yang, Shuai Sun, Danying Zhang, Chaoqin Yu
RATIONALE: Coexistence of lung adenocarcinoma and polyserous effusions is quite rare. This complexity of etiology adds difficulty to the diagnosis and is likely to cause misdiagnosis and maldiagnosis. PATIENT CONCERNS: A 43-year-old woman was admitted with symptoms of dry cough, chest suffocation, polyserous effusions, and generalized edema. Only a small number of heterocysts were detected in the ascites, and malignant cells were detected in the pleural and pericardial effusions...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28867695/development-of-a-prodrug-of-levofloxacin-to-avoid-chelation-with-al-3-and-of-pemetrexed-dimedoxomil-esters-for-oral-administration
#8
Kenji Matsuyama
 An ethoxycarbonyl 1-ethyl hemiacetal ester of levofloxacin (LVFX-EHE) avoids insoluble chelate formation with metal-containing drugs in the intestinal tract and is rapidly hydrolyzed to the parent drug. Furthermore, the minimum inhibitory concentration confirms that LVFX-EHE is less likely to cause pseudomembranous colitis because of less susceptibility to normal intestinal bacteria flora. Pemetrexed dimedoxomil, the prodrug of pemetrexed, was synthesized via reaction with medoxomil bromide after modification of L-glutamate with the tert-butyloxycarbonyl protecting group (BOC), followed by hydrolysis of the BOC moiety with trifluoroacetic acid (TFA) in CH2Cl2 at a temperature of 0°C for 2 h...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28863158/c-flip-and-the-noxa-mcl-1-axis-participate-in-the-synergistic-effect-of-pemetrexed-plus-cisplatin-in-human-choroidal-melanoma-cells
#9
Xiaofei Zhao, Feng Kong, Lei Wang, Han Zhang
Choroidal melanoma is the most common primary malignant intraocular tumor, and very few effective therapies are available to treat it. Our study aimed to understand whether pemetrexed plus cisplatin exerts a beneficial synergistic effect in human choroidal melanoma cells and to delineate the underlying molecular mechanism. To accomplish these aims, we treated choroidal melanoma cells with pemetrexed and cisplatin and assessed cell survival with SRB and MTT assays. Proteins were detected using western blotting analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28860832/a-cost-effectiveness-analysis-of-first-line-induction-and-maintenance-treatment-sequences-in-patients-with-advanced-nonsquamous-non-small-cell-lung-cancer-in-france
#10
Kaisa Taipale, Katherine B Winfree, Mark Boye, Mickael Basson, Ghassan Sleilaty, James Eaton, Rachel Evans, Christos Chouaid
BACKGROUND: Comparative effectiveness and cost-effectiveness data for induction-maintenance (I-M) sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC) are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I-M pemetrexed with those of other I-M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. MATERIALS AND METHODS: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I-M regimens most relevant to France, and incorporating French costs and resource-use data...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28860444/-nearly-complete-response-after-second-line-therapy-with-nab-paclitaxel-monotherapy-in-a-patient-with-recurrent-advanced-non-small-cell-lung-cancer
#11
Masamitsu Shimizu, Toshimichi Miya, Akihiko Takahashi, Yumiko Kobayashi, Kaoru Kubota, Akihiko Gemma, Takashi Hirose
A 62-year-old woman was diagnosed with stage IV lung adenocarcinoma. After resection of a metastatic brain tumor, she had received first-line chemotherapy consisting of 6 courses of carboplatin and pemetrexed, then 14 courses of maintenance therapy of pemetrexed until disease progression. As second-line treatment, she was administered nanoparticle albuminbound paclitaxel(nab-paclitaxel)monotherapy. A nearly complete response(nearly CR)has been maintained for 3 years without any severe adverse events. Although there is insufficient evidence for the use of nab-paclitaxel monotherapy as second-line chemotherapy, it could be an effective treatment option for patients with recurrent advanced non-small cell lung cancer...
August 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28851245/pharmacoeconomic-analysis-for-pemetrexed-as-a-maintenance-therapy-for-nsclc-patients-with-patient-assistance-program-in-china
#12
Yongji Lu, Ji Cheng, Ziyi Lin, Yuan Chen, Jianwei Xuan
OBJECTIVE: This study is to evaluate the costs, clinical efficacy, and social benefits of a patient assistance program (PAP) implemented by the China Primary Healthcare Foundation for the use of pemetrexed as a first-line non-squamous non-small cell lung cancer (NSCLC) maintenance therapy in China. METHODS: A survival analysis was conducted on the clinical data of 1,366 patients who participated in the PAP. The progression-free survival (PFS) and median maintenance treatment cycle of pemetrexed were analyzed...
September 13, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28838396/assessment-of-interfering-factors-and-clinical-risk-associated-with-discontinuation-of-pemetrexed-maintenance-therapy-in-advanced-non-squamous-non-small-cell-lung-cancer
#13
Lan Shen, Xiaomin Niu, Hong Jian, Yunhua Xu, Yongfeng Yu, Shun Lu
OBJECTIVES: Pemetrexed continuation maintenance therapy after induction with platinum-based chemotherapy is a standard treatment option for non-squamous non-small cell lung cancer (NSCLC) patients. However, discontinuation of maintenance therapy is still a challenge in clinical practice. We aimed to investigate interfering factors and clinical risk associated with discontinuation of pemetrexed maintenance therapy (PMT). MATERIALS AND METHODS: Data of patients with locally advanced or metastatic non-squamous NSCLC who received PMT between December 2011 and October 2015 were retrospectively analyzed...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28835219/clinical-decision-making-and-health-related-quality-of-life-during-first-line-and-maintenance-therapy-in-patients-with-advanced-non-small-cell-lung-cancer-nsclc-findings-from-a-real-world-setting
#14
Monika Sztankay, Johannes Maria Giesinger, August Zabernigg, Elisabeth Krempler, Georg Pall, Wolfgang Hilbe, Otto Burghuber, Maximilian Hochmair, Gerhard Rumpold, Stephan Doering, Bernhard Holzner
BACKGROUND: Maintenance therapy (MT) with pemetrexed has been shown to improve overall and progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC), without impairing patients' health-related quality of life (HRQOL) substantially. Comprehensive data on HRQOL under real-life conditions are necessary to enable informed decision-making. This study aims to (1) assess HRQOL during first-line chemotherapy and subsequent MT and (2) record patients' and physicians' reasons leading to clinical decisions on MT...
August 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28830032/novel-6-substituted-benzoyl-and-non-benzoyl-straight-chain-pyrrolo-2-3-d-pyrimidines-as-potential-antitumor-agents-with-multitargeted-inhibition-of-ts-garftase-and-aicarftase
#15
Ruijuan Xing, Hongying Zhang, Jiangsong Yuan, Kai Zhang, Lin Li, Huicai Guo, Lijuan Zhao, Congying Zhang, Shuolei Li, Tianfeng Gao, Yi Liu, Lei Wang
A novel series of 6-substituted benzoyl and non-benzoyl straight chain pyrrolo[2,3-d]pyrimidines were designed and synthesized as potential antitumor agents targeting both thymidylate and purine nucleotide biosynthesis. Starting from the key intermediate 2-amino-4-oxo-pyrrolo[2,3-d]pyrimidin-6-yl-acetic acid, target compounds 1-6 were successfully obtained through two sequential condensation and saponification reactions in decent yield. The newly synthesized compounds showed antiproliferative potencies against a panel of tumor cell lines including KB, SW620 and MCF7...
August 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28816950/pemetrexed-carboplatin-with-intercalated-icotinib-in-the-treatment-of-patient-with-advanced-egfr-wild-type-lung-adenocarcinoma-a-case-report
#16
Tongpeng Xu, Hao Wu, Shidai Jin, Huang Min, Zhihong Zhang, Yongqian Shu, Wei Wen, Renhua Guo
RATIONALE: Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. PATIENT CONCERNS: Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. DIAGNOSES: We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#17
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28806963/effectiveness-outcomes-and-health-related-quality-of-life-impact-of-disease-progression-in-patients-with-advanced-nonsquamous-nsclc-treated-in-real-world-community-oncology-settings-results-from-a-prospective-medical-record-registry-study
#18
Mark S Walker, William Wong, Arliene Ravelo, Paul J E Miller, Lee S Schwartzberg
BACKGROUND: Treatment options for advanced nonsquamous non-small cell lung cancer (NSCLC) in the first line include platinum-based doublet therapy with or without bevacizumab. This study examined efficacy outcomes and patient reported outcomes (PROs) in a community oncology patient sample. METHODS: Advanced nonsquamous NSCLC patients from 34 U.S. community oncology practices treated in first line with bevacizumab regimens (A platinum doublet; gemcitabine doublet; pemetrexed with platinum) or non-bevacizumab regimens (B platinum doublet; gemcitabine doublet; C pemetrexed with platinum) were recruited for this prospective study...
August 14, 2017: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#19
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28802835/residues-in-the-eighth-transmembrane-domain-of-the-proton-coupled-folate-transporter-slc46a1-play-an-important-role-in-defining-the-aqueous-translocation-pathway-and-in-folate-substrate-binding
#20
Srinivas Aluri, Rongbao Zhao, Andras Fiser, I David Goldman
The proton-coupled folate transporter (PCFT-SLC46A1) is required for intestinal folate absorption and folate transport across the choroid plexus. This report addresses the structure/function of the 8th transmembrane helix. Based upon biotinylation of cysteine-substituted residues by MTSEA-biotin, 14 contiguous exofacial residues to Leu316 were accessible to the extracellular compartment of the 23 residues in this helix (Leu303-Leu325). Pemetrexed blocked biotinylation of six Cys-substituted residues deep within the helix implicating an important role for this region in folate binding...
August 9, 2017: Biochimica et Biophysica Acta
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