Gefitinib-induced platelet-derived microparticle and ICAM-1 in Japanese patients with non-small cell lung cancer

Abstract

17056 Background: We recently discovered that platelet activation is observed in patients receiving gefitinib. Nomura et al. reported that activated platelets generated platelet-derived microparticle (PDMP) and this PDMP could induce adhesion molecules and an interaction between white blood cells and endothelial cells. Theaim of the present study was to identify the clinical significance between PDMP and intercellular adhesion molecule-1 (ICAM-1) in lung cancer patients receiving gefitinib. Methods: Patients with a diagnosis of non-small cell lung cancer were entered into this study. Blood samples were withdrawn before and one week and two weeks after the administration of gefitinib. PDMP and ICAM-1 were measured using an enzyme-linked immunosorbent assay kit. A total of 25 patients was recruited in the study. The characteristics of the study subjects were: age: 42–78 years (median: 68 years); gender: male vs. female = 14 vs. 11; tumor histology: adenocarcinoma vs. squamous cell carcinoma = 17 vs. 8. Nine patients were responders and the other 16 patients were non-responders. Results: The plasma concentration of PDMP significantly increased after receiving gefitinib (before vs. one week vs. two weeks = 14.1±12.0 U vs. 17.9±16.9 U (p<0.05) vs. 14.6±12.0 U n = 25). The plasma concentration of ICAM-1 significantly increased after receiving gefitinib (before vs. one week vs. two weeks = 296.2±85.1 ng/ml vs. 319.4±78.9 ng/ml vs. 344.8±74.0 ng/ml (p<0.05) n = 16). Conclusions: Platelets were activated by gefitinib therapy, and the effect of gefitinib is related to a reaction of not only blocked EGFR but also platelet activation and in part endothelial cells and leukocytes through activated platelets. The mechanisms underlying some adverse events in gefitinib-treated patients are poorly understood. Our results suggest that one of the mechanisms causing gefitinib-related adverse effects depends on platelet activation. No significant financial relationships to disclose.