Absence of epidermal growth factor receptor gene mutations in patients with hormone refractory prostate cancer not responding to gefitinib

Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in human cancers are associated with increased sensitivity to anilinoquinazoline EGFR inhibitors. To our knowledge no data have been reported on EGFR gene mutations in hormone refractory prostate cancer (HRPC). METHODS: Between March 2003 and December 2004, 23 patients with HRPC received 250 mg oral gefitinib daily in addition to antiandrogen plus luteinizing hormone-releasing hormone (LH-RH) analog for at least 2 months or until disease progression. Patients with unresected prostate cancer prospectively underwent trans-rectal biopsy of primary tumor (before starting gefitinib treatment). RESULTS: None of the patients demonstrated PSA or objective response to gefitinib. We sequenced exons 18-21 of the EGFR TK domain from genomic DNA isolated from 8 HRPC patients. No patient showed EGFR TK domain mutations. CONCLUSIONS: Our results show EGFR mutations did not occur in these patients suggesting that gefitinib is unlikely to be effective in patients with tumors not harboring specific EGFR TK domain. (c) 2007 Wiley-Liss, Inc