title: A phase II trial of gefitinib (Iressa, ZD1839) in stage IV and recurrent renal cell carcinoma.
abstract: OBJECTIVE
  The epidermal growth factor receptor (EGFR) is overexpressed in 75 to 90% of renal cell carcinomas and may play a role in tumor initiation and progression. Gefitinib (Iressa, ZD1839) is a potent, selective EGFR-tyrosine kinase inhibitor. This trial was undertaken to assess the efficacy and toxicity of gefitinib in advanced renal cell carcinoma.
  
  
  METHODS
  Oral gefitinib, 500 mg once daily, was given continuously. A single-dose reduction to 250 mg daily was allowed for toxicity. The primary end point was response rate (defined as complete remission + partial remission + stable disease). Secondary end points were progression-free survival, overall survival, toxicity, and correlation of response with EGFR status.
  
  
  RESULTS
  Twenty-one patients were enrolled on this study, and all are evaluable for response and toxicity. Patient characteristics were median age 61 (range, 35-78 years); 17 males, 4 females; median performance status 0 (range 0-2); median number of prior systemic therapies 1 (range, 0-3). The median and mean number of cycles of therapy received was 3 and 4.7 (range, 1-14+). The best response was stable disease in eight patients (38%). Median progression-free survival was 2.7 months. Median overall survival was 8.3 months. The difference in overall survival was significantly different between patients with progressive disease versus stable disease (6.1 months versus 16+ months; Log-Rank test P value < 0.0001). Three patients required a dose reduction, all for grade 3 diarrhea. There was no apparent correlation between EGFR status and stability of disease or progression of disease.
  
  
  CONCLUSIONS
  Gefitinib is without significant conventional activity in renal cell carcinoma. The relation of "stable disease" to treatment or to disease-related prognostic heterogeneity remains to be defined.
authors.affiliation: Greenebaum Cancer Center, University of Maryland, 22 South Greene Street, Baltimore, MD 21201, USA. ndawson@umm.edu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Dawson
authors.forename: Chuanfo
authors.initials: C
authors.lastname: Guo
authors.forename: Richard
authors.initials: R
authors.lastname: Zak
authors.forename: Brenda
authors.initials: B
authors.lastname: Dorsey
authors.forename: Jeanne
authors.initials: J
authors.lastname: Smoot
authors.forename: Jade
authors.initials: J
authors.lastname: Wong
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib