Tarceva1065015

Tarceva INTRODUCTION Several previous posts have discussed lung cancer, which remains the leading cause of cancer related deaths in the US. Despite its prevalence, lung cancer, particularly non-small cell lung carcinoma (NSCLC), remains resistant to chemotherapy. In recent years, angiogensis inhibitors that target the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) have proven to have some efficacy in treating NSCLC. POTENTIAL THERAPIES There are currently three targeted drugs that have been approved by the FDA for treatment of NSCLC. The first to be approved was Gefitinb, which is a selective inhibitor of the tyrosine kinase activity of EGFR and was shown in clinical trials to improve disease free survival in patients harboring EGFR mutations. The second drug to approved was Erlotinib, which also inhibits EGFR. Erlotinib is currently indicated as a second or third-line therapy in patients with advanced NSCLC. Finally, the last drug to be approved was Bevacizumab. Bevacizumab inhibits the activity of VEGF, it has no tyrosine kinase inhibitor activity, but rather is a monoclonal antibody that binds directly to the ligand making it unavailable for receptor activation. Vargatef, another tyrosine kinase inhibitor targeting VEGFR, is currently in Phase II clinical trails. Vargatef is known to have potent anti-angiogenic effects and clinical studies suggest that Vargatef will be most useful as a second line therapy for NSCLC that is unresponsive to, or relapses from, first line therapies like gefitinib. Vandetanib is a dual inhibitor of EGFR and VEGFR that is currently in clinical trials to determine its efficacy in treating NSCLC. VANDETANIB - Phase I Studies The first Phase I trial to be completed enrolled 77 patients with advanced solid tumors. The dose of 300mg/daily was well tolerated with the most common dose-dependent adverse effects including diarrhea, hypertension, and rash. The second Phase I study enrolled 18 patients and, again, used a dosage of 300mg/daily. This study demonstrated a similar toxicity and pharmacokinetic profile. Importantly, four of the nine Tarceva