[Successful individualized and targeted therapy of an NSCLC patient with Gefitinib based on a predictive assessment of the EGF-receptor mutation status].
BACKGROUND
Molecular alterations in the tyrosine kinase (TK) domain of the human epidermal growth factor receptor (EGFR) have been correlated with tumour remission upon treatment with the TK inhibitor Gefitinib in non-small cell lung cancer (NSCLC). We have retrospectively investigated the correlation of point mutations with clinical response and, based on our retrospective results, used predictive molecular assessment as the basis for treatment in one patient.


METHODS
Mutational analysis was performed in 11 NSCLC-patients (10 responders, 1 non-responder) among 62 patients treated with Gefitinib within an expanded access program.


RESULTS
Activating molecular alterations were found in 8/11 investigated samples (point mutations in exons 18 and 21, deletions in exon 19). All molecular changes were found in adenocarcinoma or bronchioloalveolar carcinoma. The tumours of two male responders with squamous cell carcinoma showed either a wild-type sequence or carried a nonsense mutation. In one patient treatment with Gefitinib after prospective assessment of mutations resulted in tumour remission and thus proved to be predictive.


CONCLUSIONS
Mutations in the EGFR TK domain correlate with the clinical response to Gefitinib. The predictive assessment of molecular alterations may thus be helpful for treatment decisions in selected cases. A clinical response to Gefitinib is nevertheless also found in patients with wild-type EGFR.
Fischer
J R
JR
Medizinische Klinik II Onkologie, Klinik Löwenstein gGmbH, Zentrum für Pneumologie und Thoraxchirurgie, 74245 Löwenstein. jr.fischer@klinik-loewenstein.de
Geiger
D
D
Haffner
U-J
UJ
Lahm
H
H
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D017384:Sequence Deletion
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib