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: 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.
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: 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.
Authors: Sheldon R Mink; Surabhi Vashistha; Wenxuan Zhang; Amanda Hodge; David B Agus; Anjali Jain Journal: Mol Cancer Res Date: 2010-06-08 Impact factor: 5.852
Authors: Courtney R Giordano; Kelly L Mueller; Laura J Terlecky; Kendra A Krentz; Aliccia Bollig-Fischer; Stanley R Terlecky; Julie L Boerner Journal: Exp Cell Res Date: 2012-06-08 Impact factor: 3.905
Authors: Angelo Di Leo; Henry L Gomez; Zeba Aziz; Zanete Zvirbule; Jose Bines; Michael C Arbushites; Stephanie F Guerrera; Maria Koehler; Cristina Oliva; Steven H Stein; Lisa S Williams; Judy Dering; Richard S Finn; Michael F Press Journal: J Clin Oncol Date: 2008-10-27 Impact factor: 44.544
Authors: E L Mayer; A H Partridge; L N Harris; R S Gelman; S T Schumer; H J Burstein; E P Winer Journal: Breast Cancer Res Treat Date: 2009-03-18 Impact factor: 4.872
Authors: Ronald A Lubet; Eva Szabo; Kenneth K Iwata; Stanley C Gill; Chris Tucker; Ann Bode; Vernon E Steele; M Margaret Juliana; Holly L Nicastro; Clinton J Grubbs Journal: Cancer Prev Res (Phila) Date: 2013-03-26