Absence of epidermal growth factor receptor gene mutations in patients with hormone refractory prostate cancer not responding to gefitinib.
BACKGROUND
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.
Curigliano
Giuseppe
G
Division of Medical Oncology, Clinical Pharmacology and New Drugs Development Unit, European Institute of Oncology and University of Milan School of Medicine, Milano, Italy. Giuseppe.curigliano@ieo.it
Pelosi
Giuseppe
G
De Pas
Tommaso
T
Renne
Giuseppe
G
De Cobelli
Ottavio
O
Manzotti
Michela
M
Spitaleri
Gianluca
G
de Braud
Filippo
F
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000235:genetics*; D000077156:Gefitinib; D006801:Humans; D008297:Male; D009154:Mutation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011799:Quinazolines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D017430:Prostate-Specific Antigen; D000077156:Gefitinib