title: A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: a Gynecologic Oncology Group study.
abstract: 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: University of New Mexico Health Sciences Center, Albuquerque, NM 87131, United States. kimberly-leslie@uiowa.edu
authors: Kimberly K
authors: KK
authors: Leslie
authors: Michael W
authors: MW
authors: Sill
authors: Edgar
authors: E
authors: Fischer
authors: Kathleen M
authors: KM
authors: Darcy
authors: Robert S
authors: RS
authors: Mannel
authors: Krishnansu S
authors: KS
authors: Tewari
authors: Parviz
authors: P
authors: Hanjani
authors: Jason A
authors: JA
authors: Wilken
authors: Andre T
authors: AT
authors: Baron
authors: Andrew K
authors: AK
authors: Godwin
authors: Russell J
authors: RJ
authors: Schilder
authors: Meenakshi
authors: M
authors: Singh
authors: Nita J
authors: NJ
authors: Maihle
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D066246:ErbB Receptors; D000077156:Gefitinib