Gefitinib (ZD1839): therapy in selected patients with non-small cell lung cancer (NSCLC)?
OBJECTIVE
To evaluate response rate, toxicity and epidermal growth factor (EGFR) mutations and gene copy number as outcome predictive factors in Italian patients with non-small cell lung cancer (NSCLC) treated with gefitinib (Iressa) in an expanded access program (EAP).


METHODS
A total of 137 patients with advanced NSCLC received gefitinib as first line treatment or after failure of chemotherapy. In 43 cases, tissue specimens were available for EGFR status evaluation: immunohistochemical (IHC) for EGFR, fluorescence in situ hybridisation (FISH) or Chromogenic in situ hybridisation (CISH)-(ISH) analysis for EGFR and HER2 gene copy number, and PCR-DNA sequencing for mutational analysis of EGFR were performed.


RESULTS
In the study population, response rate (PR) was 13%; disease stabilization (DS) 26%; overall disease control rate 39%; median survival 6.3 months and time to progression 2.7 months. Toxicity was mild (G3 skin toxicity in 3% and G3 liver toxicity in 4% of patients). An EGFR-mutation was detected in 9/43 patients: Eight deletions in exon 19 and 1 missense mutation in exon 21. Increased gene copy number for EGFR and/or HER2 was detected in 17/43 patients. Response rate was significantly higher in women, non-smokers, in mutation carriers than in wild type carriers, in EGFR-trisomy/polysomy carriers and HER2-trisomy/polysomy carriers.


CONCLUSIONS
In this study, response rate and toxicity to gefitinib treatment were consistent with previously reported data for whites. Female gender, absence of smoking history, EGFR-mutations, EGFR and HER2-polysomy were significantly associated with response to gefitinib therapy in NSCLC patients.
Dongiovanni
Diego
D
Medical Oncology, Centro Oncologico Ematologico Subalpino (C.O.E.S.), Azienda Ospedaliera S. Giovanni Battista, Turin, Italy. diego.dongiovanni@libero.it
Daniele
Lorenzo
L
Barone
Carla
C
Dongiovanni
Vincenzo
V
Fissore
Camilla
C
Sapino
Anna
A
Macrì
Luigia
L
Bussolati
Giovanni
G
Buffoni
Lucio
L
Gaspari
Fabio
F
Grillo
Raffaella
R
Birocco
Nadia
N
Addeo
Alfredo
A
Ciuffreda
Libero
L
Schena
Marina
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib