ZD1839 (Gefinitib, Iressa) In Patients With Non Small Cell Lung Cancer: A Real Promise?

ZD 1839 is a novel, low molecular weight, orally active, selective EGFR-tyrosine kinase inhibitor, which in preclinical and phase I studies has showed antitumor activity against cancers expressing EGFR. Phase I-II studies showed that ZD 1839 provides clinically significant antitumor activity in patients with pretreated NSCLC. Subsequently, phase III trials combined ZD1839 and chemotherapy in chemonaive patients with advanced NSCLC. These trials failed to demonstrate a survival advantage with the addition of ZD1839 to standard platinum-based chemotherapy. Some experts have suggested that the concomitant administration of chemotherapy and EGFR tyrosine kinase inhibitors may be antagonistic and that sequential use of these drug is a more appropriate strategy. The molecular mechanisms underlying sensitivity to ZD1839 are unknown, however recent preliminary experiences suggest that EGFR mutations may predict sensitivity to ZD1839. In any case, future trials should be conducted with appropriate correlative studies in diagnostic tumor tissue and a new possible area of clinical investigation include the use of ZD1839 in adjuvant setting.