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Pemetrexed

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https://www.readbyqxmd.com/read/29158696/65plus-open-label-study-of-bevacizumab-in-combination-with-pemetrexed-or-pemetrexed-carboplatin-as-first-line-treatment-of-patients-with-advanced-or-recurrent-nonsquamous-non-small-cell-lung-cancer
#1
Wolfgang Schuette, Claus-Peter Schneider, Walburga Engel-Riedel, Christian Schumann, Martin Kohlhaeufl, Monika Heidi Ursel Serke, Gert Hoeffken, Cornelius Kortsik, Martin Reck
Background: The aim of the study was to investigate in terms of noninferiority the efficacy and safety of a monochemotherapy regimen of pemetrexed plus bevacizumab (BevPem) versus carboplatin/pemetrexed plus bevacizumab (BevCPem) in elderly patients as first-line treatment for advanced metastatic or recurrent nonsquamous non-small-cell lung cancer (NSCLC). Materials and methods: 65Plus was a Phase III, randomized, open-label study. In total, 253 patients received BevPem (n=119) or BevCPem (n=134)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29156802/efficacy-and-safety-of-first-line-pemetrexed-plus-carboplatin-followed-by-single-agent-pemetrexed-maintenance-in-elderly-chinese-patients-with-non-squamous-non-small-cell-lung-cancer
#2
Xinmin Zhao, Hui Yu, Jing Zhao, Xianghua Wu, Si Sun, Zhiguo Luo, Huijie Wang, Jie Qiao, Jianhua Chang, Jialei Wang
Chemotherapy with pemetrexed plus carboplatin followed by pemetrexed maintenance therapy is a first-line regimen for patients with advanced non-squamous non-small-cell lung cancer. This phase II clinical study investigated the efficacy and safety of this regimen in older patients (aged ≥65 years) with advanced non-squamous non-small-cell lung cancer. All patients received 4 courses of induction therapy with pemetrexed (500 mg/m(2)) combined with carboplatin once every 3 weeks. If patients had stable disease or achieved a complete or partial tumor response after 4 courses of pemetrexed + carboplatin therapy, maintenance treatment with pemetrexed monotherapy was administered until either disease progression or intolerable toxicity occurred...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151293/-clinical-analysis-of-36-cases-of-advanced-non-small-cell-lung-cancer-nsclc-with-performance-status-ps-scores-between-2-and-4
#3
Y Y Qin, D H Zhang, X Q Lin, M Ouyang, J X Zhang, Z H Xie, Y Q Liu, S Y Li, C Z Zhou
Objective: To analyze the treatment of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4, in order to improve the diagnosis and treatment of these patients. Methods: A total of 36 patients with advanced NSCLC with hypoxemia were reviewed. The clinical data of disease characteristics, etiology, complications, manifestation, therapy, progression, and secondary biopsy were collected. The clinical efficacy was graded according to the Response Evaluation Criteria In Solid Tumors (RECIST): complete response (CR), partial response (PR), stable disease (SD) and disease progression (PD)...
November 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/29147606/temporal-and-spatial-heterogeneity-of-programmed-cell-death-1-ligand-1-expression-in-malignant-mesothelioma
#4
Simone B S P Terra, Aaron S Mansfield, Haidong Dong, Tobias Peikert, Anja C Roden
Background: Programmed Cell Death 1-Ligand 1 (PD-L1) and Programmed Death Protein 1 (PD-1) blocking antibodies are promising immunotherapies for malignancies. We have previously shown PD-L1 expression in 40% of malignant mesothelioma (MM); however, the temporal and spatial heterogeneity of its expression has not been thoroughly studied. We compared PD-L1 expression between paired primary and metastatic MM. Design: Pathology files (1995-2016) were searched for MM with tissue from multiple sites and/or time points...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147576/erlotinib-intercalating-pemetrexed-cisplatin-versus-erlotinib-alone-in-chinese-patients-with-brain-metastases-from-lung-adenocarcinoma-a-prospective-non-randomised-concurrent-controlled-trial-nct01578668
#5
Haihong Yang, Qiuhua Deng, Yuan Qiu, Jun Huang, Yubao Guan, Fengnan Wang, Xin Xu, Xinyun Yang
Objective: Erlotinib has a synergistic effect with pemetrexed for treating non-squamous non-small-cell lung cancer. We investigated the efficacy and safety of erlotinib (E) in combination with pemetrexed/cisplatin (E-P) in Chinese patients with lung adenocarcinoma with brain metastases. Design: Patients who were erlotinib-naïve or pemetrexed-naïve were assigned in parallel to receive either E or E-P. The primary endpoint was the intracranial overall response rate (ORRi)...
2017: ESMO Open
https://www.readbyqxmd.com/read/29145816/renal-failure-during-chemotherapy-renal-biopsy-for-assessing-subacute-nephrotoxicity-of-pemetrexed
#6
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/29145737/pembrolizumab-as-first-line-therapy-for-metastatic-non-small-cell-lung-cancer
#7
Martin Reck
This review describes trials evaluating the monoclonal antibody pembrolizumab (an immunotherapy that blocks the interaction between programmed death-1 and programmed death-ligand 1 and 2 [PD-L1/PD-L2]) as first-line therapy for advanced non-small-cell lung cancer (NSCLC). In the Phase III KEYNOTE-024 study, pembrolizumab monotherapy significantly improved progression-free survival (primary end point) and overall survival, and was associated with fewer adverse events compared with platinum-based chemotherapy in patients with NSCLC with PD-L1 expression on ≥50% of tumor cells...
November 17, 2017: Immunotherapy
https://www.readbyqxmd.com/read/29142786/extraordinary-clinical-benefit-to-sequential-treatment-with-targeted-therapy-and-immunotherapy-of-a-braf-v600e-and-pd-l1-positive-metastatic-lung-adenocarcinoma
#8
Shuyu D Li, Annia Martial, Alexa B Schrock, Jane J Liu
Background: The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29142753/long-term-survival-in-a-patient-with-metastatic-squamous-cell-lung-carcinoma-a-case-report
#9
Emiddio Barletta, Piera Federico, Vincenza Tinessa, Domenico Germano, Lucia Cannella, Teresa Pironti, Bruno Daniele
Non-small-cell lung cancer (NSCLC) is the most common malignancy in industrialized countries, with a 5-year survival rate of only ~15%, as the majority of the patients have advanced-stage disease at diagnosis and the treatment options are limited. Squamous cell carcinoma the second most frequent type of NSCLC and is closely associated with cigarette smoking. We herein present the case of a 72-year-old male smoker, diagnosed with stage IV squamous cell lung carcinoma, with a solitary brain metastasis. After the diagnosis, stereotactic radiotherapy was performed on the brain metastasis...
November 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29137310/ex-vivo-evaluation-of-tumor-cell-specific-drug-responses-in-malignant-pleural-effusions
#10
Carl-Olof Hillerdal, Rita Ötvös, Tünde Szatmári, Sulaf Abd Own, Gunnar Hillerdal, Åsa-Lena Dackland, Katalin Dobra, Anders Hjerpe
The effect of chemotherapy may be improved by combining the most effective drugs based on testing the sensitivity of the individual tumor ex vivo. Such estimations of tumor cells from effusions have so far not been implemented in the clinical routine as a basis for individualized choice of therapy. One obstacle for such analyses is the admixture of benign cells that might obscure the results. In this paper we test and compare two ways of performing the analysis specifically on tumor cells. First we enrich the tumor cells, using antibody labeled magnetic separation, and measure the effects of subsequent drug exposure with the metabolic activity assays WST-1 and alamar blue...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137296/early-detection-of-thymidylate-synthase-resistance-in-non-small-cell-lung-cancer-with-flt-pet-imaging
#11
Xiao Chen, Yizeng Yang, Sharyn Katz
Introduction: Inhibition of thymidylate synthase (TS) results in a transient compensatory "flare" in thymidine salvage pathway activity measureable with (18)F-thymidine (FLT)- positron emission tomography (PET) at 2hrs. of therapy which may predict non-small cell lung cancer (NSCLC) sensitivity to TS inhibition. Materials and Methods: Resistance to TS inhibition by pemetrexed was induced in NSCLC cell lines H460 and H1299 through TS overexpression. TS overexpression was confirmed with RT-PCR and Western blotting and pemetrexed resistance confirmed with IC50 assays...
October 10, 2017: Oncotarget
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
#12
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/29128428/clinical-and-translational-implications-of-ret-rearrangements-in-non-small-cell-lung-cancer
#13
REVIEW
Roberto Ferrara, Nathalie Auger, Edouard Auclin, Benjamin Besse
Since the discovery in 2012 of RET rearrangements in non-small cell lung cancer (NSCLC), at least 12 different fusion variants have been identified, with KIF5B-RET being the most frequent and the best characterized. Unlike ALK and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry, although fluorescence in situ hybridization and reverse transcriptase PCR are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histology, never-smoking status, younger age, more advanced stage disease, potentially higher chemo-sensitivity (in particular to pemetrexed-based regimens), and coexistence of other genomic alterations...
November 8, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29127457/the-promise-and-challenges-of-exploiting-the-proton-coupled-folate-transporter-for-selective-therapeutic-targeting-of-cancer
#14
REVIEW
Larry H Matherly, Zhanjun Hou, Aleem Gangjee
This review considers the "promise" of exploiting the proton-coupled folate transporter (PCFT) for selective therapeutic targeting of cancer. PCFT was discovered in 2006 and was identified as the principal folate transporter involved in the intestinal absorption of dietary folates. The recognition that PCFT was highly expressed in many tumors stimulated substantial interest in using PCFT for cytotoxic drug targeting, taking advantage of its high level transport activity under the acidic pH conditions that characterize many tumors...
November 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29124473/severity-and-predictive-factors-of-adverse-events-in-pemetrexed-containing-chemotherapy-for-non-small-cell-lung-cancer
#15
Tsuyoshi Miyahara, Naoko Sueoka-Aragane, Kentaro Iwanaga, Norio Ureshino, Kazutoshi Komiya, Tomomi Nakamura, Chiho Nakashima, Tomonori Abe, Hisashi Matsunaga, Shinya Kimura
Pemetrexed is a key anticancer agent for treatment of advanced non-small cell lung cancer (NSCLC). Pemetrexed is generally well tolerated, but individual-patient differences exist in severity of adverse events. Our study aimed to characterize the adverse events of pemetrexed that result in discontinuation of chemotherapy and to identify risk factors associated with those adverse events. We retrospectively studied the incidence of adverse events in 257 patients with NSCLC who received pemetrexed (P) with or without bevacizumab (B) and/or carboplatin (C): P, PB, CP, or CPB...
November 9, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29117941/loss-of-uracil-dna-glycosylase-selectively-re-sensitizes-p53-mutant-and-deficient-cells-to-5-fdu
#16
Yan Yan, Yulan Qing, John J Pink, Stanton L Gerson
Thymidylate synthase (TS) inhibitors including fluoropyrimidines [e.g., 5-Fluorouracil (5-FU) and 5-Fluorodeoxyuridine (5-FdU, floxuridine)] and antifolates (e.g., pemetrexed) are widely used against solid tumors. Previously, we reported that shRNA-mediated knockdown (KD) of uracil DNA glycosylase (UDG) sensitized cancer cells to 5-FdU. Since p53 has also been shown as a critical determinant of the sensitivity to TS inhibitors, we further interrogated 5-FdU cytotoxicity after UDG depletion with regard to p53 status...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29116477/4egi-1-represses-cap-dependent-translation-and-regulates-genome-wide-translation-in-malignant-pleural-mesothelioma
#17
Arpita De, Blake A Jacobson, Mark S Peterson, Joe Jay-Dixon, Marian G Kratzke, Ahad A Sadiq, Manish R Patel, Robert A Kratzke
Deregulation of cap-dependent translation has been implicated in the malignant transformation of numerous human tissues. 4EGI-1, a novel small-molecule inhibitor of cap-dependent translation, disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex. The effects of 4EGI-1-mediated inhibition of translation initiation in malignant pleural mesothelioma (MPM) were examined. 4EGI-1 preferentially inhibited cell viability and induced apoptosis in MPM cells compared to normal mesothelial (LP9) cells...
November 8, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29114329/structural-diversity-in-the-host-guest-complexes-of-the-antifolate-pemetrexed-with-native-cyclodextrins-gas-phase-solution-and-solid-state-studies
#18
Magdalena Ceborska, Magdalena Zimnicka, Aneta Aniela Kowalska, Kajetan Dąbrowa, Barbara Repeć
The complexation of the antifolate pemetrexed (PTX) with native cyclodextrins was studied. This process, along with the findings gathered for the structurally related folic acid was treated as a model for exploiting host-guest interactions of this class of guest molecules in the gas phase, in solution and in the solid state. Mass spectrometry was employed for the investigation of the architecture and relative gas-phase stabilities of these supramolecular complexes. The mode of complexation was further tracked by 1D and 2D NMR proving the formation of the exclusion-type complex with α-CD and pseudorotaxane inclusion-type complexes with β-, and γ-CDs...
2017: Beilstein Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29104613/impact-of-exon-19-versus-exon-21-egfr-activating-mutation-on-outcomes-with-upfront-pemetrexed-carboplatin-chemotherapy
#19
Vanita Noronha, Vijay Patil, Amit Joshi, Anuradha Chougule, Atanu Bhattacharjee, Rajiv Kumar, Sucheta More, Supriya Goud, Ashay Karpe, Anant Ramaswamy, Nikhil Pande, Arun Chandrasekharan, Alok Goel, Vikas Talreja, Abhishek Mahajan, Amit Janu, Nilendu Purandare, Kumar Prabhash
Background: EGFR mutation subtype is a recognised factor impacting outcomes of patients receiving oral tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Evidence for the effect of this factor on outcomes in patients receiving pemetrexed is limited. Methods: We completed a study comparing pemetrexed-platinum combination versus oral TKI in EGFR mutation-positive patients in lung cancer. We analysed the impact of EGFR mutation subtype, specifically, exon 19 and 21 on the PFS and OS of patients treated with pemetrexed (500 mg/m(2) on day 1) and carboplatin (AUC 5 on day 1) as first-line therapy...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/29101518/phase1-study-of-cisplatin-plus-pemetrexed-with-erlotinib-and-bevacizumab-for-chemotherapy-na%C3%A3-ve-advanced-non-squamous-non-small-cell-lung-cancer-with-egfr-mutations
#20
Motohiro Tamiya, Akihiro Tamiya, Takayuki Shiroyama, Sawa Takeoka, Yujiro Naito, Naoki Omachi, Yohei Kimura, Naoko Morishita, Hidekazu Suzuki, Norio Okamoto, Kyoichi Okishio, Tomoya Kawaguchi, Shinji Atagi, Tomonori Hirashima
Background Cisplatin and pemetrexed are very effective against advanced non-squamous non-small cell lung cancer (NSCLC) without EGFR mutations. Erlotinib plus bevacizumab are highly effective against advanced NSCLCs with activating EGFR mutations. We performed this phase I 'Quartet Trial' to determine the safety and efficacy of all 4 agents as a first-line treatment for non-squamous NSCLC patients harboring activating EGFR mutations. Patients and Methods Patients received escalating quartet-agent doses every 3 weeks for 4 cycles...
November 4, 2017: Investigational New Drugs
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