Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer

Abstract

Antibodies targeting epidermal growth factor receptor (EGFR) have proven to be effective in patients with nonsmall cell lung cancer (NSCLC) that express EGFR. We recently published a phase I study of weekly matuzumab plus paclitaxel. This therapy was well tolerated and showed clinical responses in the majority of patients. Although matuzumab displays potent antitumor activity in some patients, not all patients respond well to treatment. Whether dysregulation of EGFR-mediated pathways precludes or sensitizes cells to paclitaxel is unknown. We sought to determine molecular predictive factors for therapy response in a phase

RETRACTED ARTICLE: Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer

“…CS and the surface modifications of NPs with CS offer various advantages: extended release drug delivery systems with mucoadhesive nature thus enhancing the drug absorption and prolongation of drug release [8], decreased burst release of drug due to CS coating as well as enhanced retention and permeation of NPs due to affinity between positively charged CS and negatively charged membrane [15,16]. Docetaxel (DTX) exhibits a wide range of anticancer activity against: breast cancer [17], ovarian cancer [18], non-small cell lung carcinoma [19] and melanoma [20], prostate cancer [21], pancreatic cancer [22] as well as advanced head and neck cancer [23]. However, taxanes does not offer the advantage of oral treatment (ease of administration and improved patient compliance) due to various factors: limited aqueous solubility and dissolution hence low oral bioavailability, affinity to the membrane-bound drug efflux pump Pglycoprotein (P-gp) [24] and metabolism by cytochrome P450 3A4 [25].…”

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

“…Overall response rate of matuzumab combined with paclitaxel, as first line therapy, was 22%. EGFR expression and the KRAS mutation status seemed to predict a clinical response to matuzumab [110]. Pemetrexed/matuzumab as second line therapy seemed to be superior to chemotherapy alone (objective response 11% vs 5%) but difference was not statistically significant probably due to low patient inclusion (n = 148) [111].…”

Predictive and Prognostic Biomarkers for Patients Treated with Anti-EGFR Agents in Lung Cancer: A Systemic Review and Meta-Analysis

“…A total of 61 (Eberhard et al, 2005;Fujimoto et al, 2005;Pao et al, 2005;Endoh et al, 2006;Giaccone et al, 2006;Han et al, 2006;Hirsch et al, 2006;Cappuzzo et al, 2007;Hirsch et al, 2007;Ichihara et al, 2007;Jackman et al, 2007;Loprevite et al, 2007;Massarelli et al, 2007;van Zandwijk et al, 2007;Chang et al, 2008;D'Addario et al, 2008;Felip et al, 2008;Kalikaki et al, 2008;Miller et al, 2008;Sasaki et al, 2008;Schneider et al, 2008;Wu et al, 2008;Zucali et al, 2008;Boldrini et al, 2009;Jackman et al, 2009;Lara-Guerra et al, 2009;Marchetti et al, 2009;Pesek et al, 2009;Schittenhelm et al, 2009;Douillard et al, 2010;Khambata-Ford et al, 2010;Lind et al, 2010;Price et al, 2010;Ready et al, 2010;Tiseo et al, 2010;Wang et al, 2010;ZHU Yu-jia et al, 2010;Brugger et al, 2011;Dahabreh et al, 2011;Dingemans et al, 2011;Fidler et al, 2011;Hirsch et al, 2011...…”