Affiliation:
1. From the Vall d'Hebron University Hospital; Hospital Clinic, Barcelona; Instituto Valenciano de Oncologia; Universitat de Valencia, Hospital Clínico Universitario de Valencia and CESAT Valencia, Spain; and AstraZeneca, Wilmington, DE
Abstract
Purpose To evaluate the antitumor activity and pharmacodynamic/biologic effect of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced breast cancer. Methods In this phase II multicenter trial, the primary objective was assessment of the tumor response rate with gefitinib; secondary objectives included analysis of the pharmacodynamic and biologic profiles in healthy and tumor tissue. Results Of 31 assessable patients, 12 (38.7%) had stable disease, including 3 (9.7%) with recurrent breast cancer that stabilized for ≥ 6 months. No complete or partial responses were observed. Pretreatment tumor samples were available in all patients. In addition, paired baseline and on-treatment (day 28) assessable skin and tumor biopsies were available in 27 and 16 patients, respectively. Sequential immunohistochemical studies in skin and tumor biopsies demonstrated complete inhibition of epidermal growth factor receptor (EGFR) phosphorylation in both healthy and malignant tissues. The downstream consequences of receptor blockade were distinct in skin and tumor samples: while phosphorylation of mitogen-activated protein kinase was inhibited in both tissues, gefitinib treatment induced p27 and a decrease in Ki67 in skin but not in tumors. Furthermore, gefitinib did not inhibit the activated form of Akt in the tumors. Conclusion This study demonstrates a good correlation between the degree of inhibition of EGFR in skin and in breast tumors. The lack of significant clinical activity of gefitinib in our study population is not due to lack of receptor inhibition in these tumors but rather to lack of EGFR dependence in the tested population.
Publisher
American Society of Clinical Oncology (ASCO)
Cited by
310 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献