Search results for "pemetrexed"
showing 10 items of 26 documents
Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells
2016
Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and res…
Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A co…
2020
Abstract Background Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. Methods Modulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was determined in tissue microarrays of radically resected malignant pleural mesothelioma (MPM, N = 33) and diffuse peritoneal mesothelioma (DMPM, N = 56) patients. Results Overexpression of hypoxia…
Abstract B072: Phase Ib trial of the RNActive cancer vaccine BI 1361849 (CV9202) and local radiotherapy in patients with stage IV non-small cell lung…
2016
Abstract Background: Preclinical studies demonstrated that local radiotherapy (RT) acts synergistically with RNActive mRNA vaccines to enhance anti-tumor effects and increase tumor-infiltrating lymphocytes. BI 1361849 is a therapeutic vaccine comprising optimized mRNA constituents encoding six NSCLC-associated antigens. Interim data of a phase Ib study, employing local RT to increase the immune mediated tumor control by BI 1361849, have been previously published (J Clin Oncol 34, 2016, suppl; abstr e20627). Here we report results of immune response analyses as well as updated safety and efficacy data. Methods: Patients (pts) with stage IV NSCLC were enrolled in three cohorts based on histol…
Third-line therapy for advanced non-small-cell lung cancer patients: a feasible therapeutic option?
2010
Two decades ago best supportive care was considered a valid therapeutic option for advanced non-small cell lung cancer (NSCLC) patients until the evidence derived from meta-analysis showed symptom improvement and a survival advantage from systemic chemotherapy. A further advantage was reported when docetaxel and pemetrexed were used as second-line treatment after failure of first-line platinum-based chemotherapy. Furthermore, the biologic therapies targeting the epidermal growth factor receptor – erlotinib and gefitinib – have modified the therapeutic approach to second- and third-line treatment of NSCLC patients. In fact, to date, erlotinib is the only drug to be licensed for third-line th…
Phase II study of pemetrexed (Pem) and cisplatin (Cis) plus cetuximab (Cet) followed by Pem and Cet maintenance therapy in patients (Pts) with advanc…
2012
7554 Background: A prospective, nonrandomized, multicenter study was conducted to assess the effect of adding cet to pem and cis in pts with advanced nonsquamous NSCLC. Methods: 113 Caucasian performance status 0-1 pts received 1st line pem (500 mg/m2) and cis (75 mg/m2) on day 1 (21d cycle) for 4-6 cycles and cet (400 mg/m2 loading dose followed by 250 mg/m2) weekly. Non-progressive pts received pem 500 mg/m2 on day 1 (21d cycle) plus cet (250mg/m2 weekly) until progression. Pts received vitamin B12/folic acid and dexamethasone. Primary endpoint was objective response rate (ORR) (RECIST 1.0). Secondary endpoints were progression free survival (PFS), 1 year survival rate, translational res…
Farletuzumab for NSCLC: Exploiting a well-known metabolic pathway for a new therapeutic strategy
2015
Abstract: Introduction: The therapeutic options for NSCLC are limited barring targeted drugs, such as EGFR tyrosine-kinase inhibitors and anaplastic lymphoma kinase inhibitors, for patients bearing oncogenic mutations. Platinum-based chemotherapy remains the best strategy for most patients. New targeted drugs, including mAbs and small molecules, are currently under clinical investigation for treating NSCLC patients. Areas covered: The authors of this article focus on farletuzumab, a mAb targeting folate receptor, which has been studied in ovarian cancer and various other malignancies. In this review, the authors review its potential as therapy for NSCLC, because of the biological rationale …
Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer.
2010
Introduction This randomized phase II study investigated pemetrexed in combination with the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer. Methods Patients received pemetrexed 500 mg/m 2 every 3 weeks either alone ( n = 50) or in combination with matuzumab at either 800 mg weekly ( n = 51) or 1600 mg every 3 weeks ( n = 47). The primary end point was objective response, as assessed by an independent review committee. Results Tumor EGFR expression was detected in 87% of randomized patients. The objective response rate for the pooled matuzumab-treated a…
Circulating miR-22, miR-24 and miR-34a as novel predictive biomarkers to pemetrexed-based chemotherapy in advanced non small cell lung cancer
2013
Pemetrexed has been widely used in patients with advanced non-small cell lung cancer (NSCLC). The clinical relevance of polymorphisms of folate pathway genes for pemetrexed metabolism have not been fully elucidated yet. The aim of this study was to evaluate the expression levels of circulating miR-22, miR-24, and miR-34a, possibly involved in folate pathway, in NSCLC patients treated with pemetrexed compared with healthy controls and to investigate their impact on patient clinical outcomes. A total of 22 consecutive patients with advanced NSCLC, treated with pemetrexed-based chemotherapy and 27 age and sex matched healthy controls were included in this preliminary analysis. miR-22, miR-24, …
Does an optimal therapeutic sequence exist in advanced non-small cell lung cancer?
2008
A growing percentage of patients affected by advanced non-small cell lung cancer who progressed after first-line chemotherapy still have a good performance status and require second-line treatment.An overview of the state of the art of second-line therapeutic options is presented.The scope of the review is to give an update on the therapeutic options currently available for the second-line treatment of patients with advanced non-small cell lung cancer.Among chemotherapeutic drugs docetaxel and pemetrexed have been approved for second-line treatment of advanced non-small cell lung cancer. Although the drugs are equiactive in terms of response rate and survival parameters the latter has a cle…
Adding chemotherapy to TKI: Can we improve first-line treatment for EGFR-mutated NSCLC patients?
2016
In The Journal of Clinical Oncology , Ying Cheng and colleagues (1) have recently reported the results of a phase II randomized trial comparing pemetrexed plus gefitinib vs. gefitinib in treatment-naive, East Asian patients, with advanced non-squamous non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations. The study met its primary end-point in the intent-to-treat population, showing a significantly longer median progression free survival (PFS) in favors of the combination arm (15.8 months) compared to single agent arm (10.9 months) [hazard ratio (HR): 0.68; 95% CI, 0.48 to 0.96; one-sided P=0.014; two-sided P=0.029].