Gefitinib: current status in the treatment of non-small cell lung cancer

Gefitinib (Iressa) is a novel drug approved in 28 countries (as of June 2004), including Japan, the US, Canada and Australia as second- and third-line monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer refractory to prior chemotherapy. Gefitinib is an orally active, epidermal growth factor receptor (EGFR)-tyrosine kinase (EGFR-TK) reversible inhibitor which blocks EGFR phosphorylation and subsequent signal transduction pathways involved in proliferation, metastasis, angiogenesis and apoptosis inhibition. Recently, mutations in the TK domain of the EGFR have been identified in those patients with refractory non-small cell lung cancer who achieved dramatic tumor responses to gefitinib. Although the role of EGFR-TK mutation status in predicting other clinical benefits with gefitinib, i.e. disease stabilization and symptom improvement, is unclear, these findings, along with increasing knowledge of other potential biomarkers of response, are significant developments towards further optimizing the use of gefitinib. Gefitinib has favorable pharmacokinetic and pharmacodynamic properties and low toxicity. No dosage adjustment is required for patient age, body weight, gender, ethnicity or moderate to severe hepatic impairment due to liver metastases. Several clinical studies on gefitinib as monotherapy have demonstrated clinically significant symptom relief, tumor response and good tolerability after failure of chemotherapy-based treatment in non-small cell lung cancer. These studies led to gefitinib approval in many countries as a new therapeutic option for patients with advanced non-small cell lung cancer that failed prior chemotherapy. In contrast to the clinical benefit imparted by gefitinib as monotherapy in patients previously treated with chemotherapy, gefitinib in combination with standard platinum-based chemotherapy in chemonaive patients did not improve either survival or other clinical endpoints in non-small cell lung cancer. This review provides currently available data from clinical studies on gefitinib as monotherapy or in combination with platinum-containing chemotherapy.