Gefitinib: a review of its use in the treatment of locally advanced/metastatic non-small cell lung cancer.

摘要: Gefitinib (Iressa™) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that offers treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), in particular those who are harbouring EGFR mutations. In a large phase III trial (IPASS) chemotherapy-naive Asian adenocarcinoma were never smokers former light smokers, oral gefitinib was more effective than carboplatin plus paclitaxel prolonging progression-free survival (PFS). prespecified subgroup analysis, EGFR-mutation-positive status associated positive response to treatment. Furthermore, NSCLC restricted mutations found recipients had significantly longer PFS recipients. trials (INTEREST, V-15-32) unselected, previously treated patients, the overall (OS) noninferior to, not different from, of docetaxel placebo-controlled (ISEL), pre-planned analyses and non-smokers showed these subgroups prolonged OS, biomarkers predicted gefitinib. also greater improvements quality life (QOL) both patients. A head-to-head versus erlotinib would help position relative this population. Further research required identify factors non-response EGFR-tyrosine-kinase inhibitors generally well tolerated treatment, rash diarrhoea being most common treatment-emergent adverse events. Interstitial disease (ILD) serious co-morbidity other treatments; ILD-type events occurred incidence ≈1% participating clinical trials, Notably, fewer haematological neurological effects comparator chemotherapy regimens. as monotherapy Pharmacological The presumed mechanism action through inhibition Properties kinase, thereby blocking downstream signalling processes activate proliferation, migration, angiogenesis survival. Inhibitory on occur at concentrations below achieved recommended dosage. Mutations domain correlated sensitivity inhibitors. After administration, relatively slowly absorbed, time peak concentration 3-7 hours. healthy adults, single doses up including 250 mg, increases systemic exposure dose-proportional. bioavailability solid tumours 59%. penetrates tumour tissues, reaching high 42- 60-fold plasma.