A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study

Kimberly K Leslie; Michael W Sill; Edgar Fischer; Kathleen M Darcy; Robert S Mannel; Krishnansu S Tewari; Parviz Hanjani; Jason A Wilken; Andre T Baron; Andrew K Godwin; Russell J Schilder; Meenakshi Singh; Nita J Maihle

doi:10.1016/j.ygyno.2013.02.019

Back

A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study

Journal article

Open access

Peer reviewed

A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study

Kimberly K Leslie, Michael W Sill, Edgar Fischer, Kathleen M Darcy, Robert S Mannel, Krishnansu S Tewari, Parviz Hanjani, Jason A Wilken, Andre T Baron, Andrew K Godwin, …

Gynecologic Oncology, Vol.129(3), pp.486-494

06/2013

DOI: 10.1016/j.ygyno.2013.02.019

PMCID: PMC3700732

PMID: 23438670

Files and links (1)

url

https://doi.org/10.1016/j.ygyno.2013.02.019View

Published (Version of record) Open Access

Abstract

A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. 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. Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥6months, 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. 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. ► Gefitinib was evaluated in a phase II trial of advanced endometrial cancer. ► One patient achieved a complete response, though gefitinib did not demonstrate significant clinical activity overall. ► The levels of a soluble truncated form of EGFR, sEGFR, positively correlated with overall survival.

Endometrial Cancer

Estrogen receptor

Gefitinib

Progesterone receptor

Soluble EGFR

Epidermal growth factor receptor (EGFR)

Details

Title: Subtitle: A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study
Creators: Kimberly K Leslie - University of New Mexico Health Sciences Center, Albuquerque, NM 87131, United States
Michael W Sill - Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States
Edgar Fischer - University of New Mexico Health Sciences Center, Albuquerque, NM 87131, United States
Kathleen M Darcy - Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States
Robert S Mannel - University of Oklahoma; Health Sciences Center, Oklahoma City, OK 73190, United States
Krishnansu S Tewari - University of California Medical Center Irvine, Orange, CA 92868, United States
Parviz Hanjani - Hanjani Institute for Gynecologic Oncology; Abington Memorial Hospital, Abington, PA 19001, United States
Jason A Wilken
Andre T Baron - University of Kentucky, Lucille P. Markey Cancer Center, Lexington, KY 40536, United States
Andrew K Godwin - Fox Chase Cancer Center; Philadelphia, PA 19111, United States
Russell J Schilder - Fox Chase Cancer Center; Philadelphia, PA 19111, United States
Meenakshi Singh - Stony Brook University Hospital and School of Medicine, Stony Brook, NY 11794, United States
Nita J Maihle - Yale University School of Medicine, New Haven, CT 06520, United States
Resource Type: Journal article
Publication Details: Gynecologic Oncology, Vol.129(3), pp.486-494
DOI: 10.1016/j.ygyno.2013.02.019
PMID: 23438670
PMCID: PMC3700732
NLM abbreviation: Gynecol Oncol
ISSN: 0090-8258
eISSN: 1095-6859
Publisher: Elsevier Inc
Grant note: Barbara Beach Fund CA 27469 / National Cancer Institute Marsha Rivkin Foundation for Ovarian Cancer Research Susan G Komen for the Cure CA 37517; R01-CA099908; R01-CA140323; R01-CA79808 / GOG Statistical and Data Center
Language: English
Date published: 06/2013
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983931696002771

Metrics

40 Record Views

43 Times Cited - Web of Science