Gefitinib (IressaTM, ZD1839) and Tyrosine Kinase Inhibitors

Publisher Website
Google Scholar
Abstract
Targeted therapies are one of the latest innovative trends in cancer therapy. The epidermal growth factor receptor (EGFR) is a target found in high concentrations in several solid tumors including lung, breast, colorectal, and brain. Tyrosine kinase inhibitors, such as gefitinib (Iressa, ZD1839), block the EGFR. As a result, there is inhibition of cellular proliferation, promotion of apoptosis, and inhibition of anti-angiogenesis. Gefitinib has demonstrated significant efficacy in non-small-cell lung cancer (NSCLC), leading to FDA approval for treatment of this refractory disease. Phase 2 trials with gefitinib for platinum refractory NSCLC reported disease response and symptom improvement. Early results of phase 2 studies of gefitinib, combined with standard chemotherapy in colorectal cancer, showed a 75% response rate compared with 55% with standard therapy alone. Gefitinib, combined with flutamide, produced an additive growth inhibition in prostate cancer. A phase 2 trial of gefitinib in first-relapse glioblastoma multiforme demonstrated median overall survival from treatment start of 39.4 weeks compared with 40 weeks with standard chemotherapy. Gefitinib is an oral agent with a mild toxicity profile, and thus, may be an optimal addition to chemotherapeutic regimens for some solid tumors. Gefitinib is potentially a vital and useful weapon in the arsenal of cancer therapies.