BACKGROUND: A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. METHODS: Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment. EGFR was sequenced, and serum concentrations of soluble EGFR (sEGFR) at baseline also were examined. RESULTS: Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥6 months, and one had a complete response which was not associated with an EGFR mutation. The concentration of sEGFR in pretreatment serum was positively correlated with overall survival (OS), but not with responsiveness to gefitinib in this small patient cohort. Expression of tumor biomarkers was not associated with PFS or OS. Co-expression of ER with PRA in primary and recurrent tumors, and pEGFR with pERK in primary tumors was observed. CONCLUSIONS: This treatment regimen was tolerable but lacked sufficient efficacy to warrant further evaluation in this setting. The possible association between serum sEGFR concentrations and OS, and temporal changes in expression of pEGFR and pERK and the documented CR of one patient are interesting and warrant additional investigation.
BACKGROUND: A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. METHODS:Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment. EGFR was sequenced, and serum concentrations of soluble EGFR (sEGFR) at baseline also were examined. RESULTS: Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥6 months, and one had a complete response which was not associated with an EGFR mutation. The concentration of sEGFR in pretreatment serum was positively correlated with overall survival (OS), but not with responsiveness to gefitinib in this small patient cohort. Expression of tumor biomarkers was not associated with PFS or OS. Co-expression of ER with PRA in primary and recurrent tumors, and pEGFR with pERK in primary tumors was observed. CONCLUSIONS: This treatment regimen was tolerable but lacked sufficient efficacy to warrant further evaluation in this setting. The possible association between serum sEGFR concentrations and OS, and temporal changes in expression of pEGFR and pERK and the documented CR of one patient are interesting and warrant additional investigation.
Authors: G Scambia; P Benedetti Panici; G Ferrandina; F Battaglia; M Distefano; G D'Andrea; R De Vincenzo; F Maneschi; F O Ranelletti; S Mancuso Journal: Int J Cancer Date: 1994-01-02 Impact factor: 7.396
Authors: F Calero; E Asins-Codoñer; J Jimeno; F Rodriguez Escudero; J Mendaña; J Iglesias; F Matía; A Armas; R Díaz-Castellanos; J Garzón Journal: Eur J Cancer Date: 1991 Impact factor: 9.162
Authors: Kathleen N Moore; Michael W Sill; Meaghan E Tenney; Christopher J Darus; David Griffin; Theresa L Werner; Peter G Rose; Robert Behrens Journal: Gynecol Oncol Date: 2015-07-11 Impact factor: 5.482
Authors: Henry D Reyes; Kristina W Thiel; Matthew J Carlson; Xiangbing Meng; Shujie Yang; Jean-Marie Stephan; Kimberly K Leslie Journal: Mol Diagn Ther Date: 2014-04 Impact factor: 4.074
Authors: David Bender; Michael W Sill; Heather A Lankes; Henry D Reyes; Christopher J Darus; James E Delmore; Jacob Rotmensch; Heidi J Gray; Robert S Mannel; Jeanne M Schilder; Mark I Hunter; Carolyn K McCourt; Megan I Samuelson; Kimberly K Leslie Journal: Gynecol Oncol Date: 2015-07-15 Impact factor: 5.482
Authors: Matthew A Powell; Michael W Sill; Paul J Goodfellow; Doris M Benbrook; Heather A Lankes; Kimberly K Leslie; Yvette Jeske; Robert S Mannel; Monique A Spillman; Paula S Lee; James S Hoffman; D Scott McMeekin; Pamela M Pollock Journal: Gynecol Oncol Date: 2014-07-11 Impact factor: 5.482
Authors: Vicky Makker; Virginia L Filiaci; Lee-May Chen; Christopher J Darus; James E Kendrick; Gregory Sutton; Katherine Moxley; Carol Aghajanian Journal: Gynecol Oncol Date: 2015-04-16 Impact factor: 5.482
Authors: Kimberly K Leslie; Kristina W Thiel; Henry D Reyes; Shujie Yang; Yuping Zhang; Matthew J Carlson; Nirmala S Kumar; Donghai D Dai Journal: Obstet Gynecol Int Date: 2013-10-07