Pharmacodynamic Studies of Gefitinib in Tumor Biopsy Specimens From Patients With Advanced Gastric Carcinoma

• DOI: 10.1200/jco.2005.04.2424
• Publication Date: 2006-09-08T22:29:43Z
• Authors: Federico Rojo; Josep Tabernero; Joan Albanell; Eric Van Cutsem; Atsushi Ohtsu; Toshihiko Doi; Wasaburo Koizumi; Kuniaki Shirao; Hiroya Takiuchi; S. Ramon Cajal; José Baselga
• Keywords: Adult; Aged, 80 and over; Male; Mitogen-Activated Protein Kinase Kinases; Carcinoma; Antineoplastic Agents; Apoptosis; Gefitinib; Middle Aged; 3. Good health; ErbB Receptors; 03 medical and health sciences; Ki-67 Antigen; 0302 clinical medicine; Area Under Curve; Biomarkers, Tumor; Quinazolines; Humans; Female; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Aged; Signal Transduction

Epidermal growth factor receptor (EGFR) is highly expressed in some gastric cancers and implicated cancer cell proliferation. The objective of this study was to assess the situ biologic activity EGFR tyrosine kinase inhibitor gefitinib tumor samples a phase II study.Patients with previously treated stage IV adenocarcinoma stomach or gastroesophageal junction were randomly assigned receive (250 500 mg/d). Tumor biopsies, obtained at screening on day 28 treatment, assessed for biomarker expression using immunohistochemistry analysis apoptosis.One hundred sixteen from 70 patients available, baseline 46 on-therapy biopsies. At baseline, levels significantly correlated phosphorylated (pEGFR; P < .001) Ki67 (P = .011), but not mitogen-activated protein (pMAPK). After pEGFR cells reduced .001); case pMAPK Akt (pAkt). However, cases inhibited pAkt these tumors had enhanced apoptosis. Likewise, there significant correlation between increased exposure geftinib apoptosis.Gefitinib reached concentrations sufficient inhibit activation advanced carcinoma patients, although did translate into clinical benefit. Overall, intratumoral phosphorylation MAPK by gefitinib. finding that decreases apoptosis deserves further exploration.