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Pharmacotherapeutic group: Antineoplastic, protein kinase inhibitors. ATC code: L01XE02.
Pharmacology: Pharmacodynamics: Gefitinib is a selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, commonly expressed in solid human tumours of epithelial origin. Inhibition of EGFR tyrosine kinase activity inhibits tumour growth, metastasis and angiogenesis and increases tumour cell apoptosis.
Patients that have never smoked, have adenocarcinoma histology, are female gender or are of Asian ethnicity, are more like to benefit from treatment with GEFITERO. These clinical characteristics are also associated with a higher rate of EGFR mutation positive tumours.
Pharmacokinetics: This study was designed as an open label, balanced, randomized, two-treatment, two-sequence, two-period, single oral dose, crossover bioequivalence study in normal, healthy adult human male subjects under fasting conditions. The study was conducted following an oral administration of one tablet 250 mg of the test drug or one tablet 250 mg of the product drug.
Based on the pharmacokinetic parameters of Gefitinib (N = 53), geometric least squares means for Test drug and Reference drug showed: Cmax values were 188.861 and 174.723, respectively; AUC0-96 values were 5650.393 and 5302.900, respectively.
Relative bioavailability results for Gefitinib (N = 53) were as following : The 90% Confidence Intervals for the ratio of geometric least squares means was found to be 96.57 - 120.98% for Cmax and 100.40 - 113.08% for AUC0-96. Intra subject CV (%) of Cmax and AUC0-96 for Gefitinib were 35.7 and 18.4%, respectively.
Conclusion: These results showed that 250 mg Gefitinib film coated tablet was bioequivalent to the reference product.
Resistance: Most NSCLC tumors with sensitizing EGFR kinase mutations eventually develop resistance to Gefitinib treatment with a median time to disease progression of 1 year. In about 60% of cases, resistance is associated with a secondary T790M mutation for which T790M targeted EGFR TKIs may be considered as a next line treatment option. Other potential mechanism of resistance have been reported following treatment with EGFR signal blocking agents including bypass signaling such as HER2 and MET gen amplification and PIK3CA mutations. Phenotypic switch to small cell lung cancer has also been reported.
