New targets and new treatments in non-small cell lung cancer

New agents directed against molecular targets have now been tested in large prospectively randomized clinical trials for patients with untreated advanced non-small cell lung cancer (NSCLC). The trials have included small molecule inhibitors of receptor tyrosine kinases (gefitinib and erlontinib), monoclonal antibodies directed against either the ligands (bevicizumab against vascular endothelial growth factor) or their receptors (trastuzumab against ErbB2) and antisense nucleotides directed against mRNA coding for molecular targets (ISIS 3521 against protein kinase C alpha). The largest mature trials have included agents directed against ErbB1 (epidermal growth factor receptor). Two different small molecule inhibitors of erbB1 (gefitinib and erlontinib) and have been tested in 4 large international randomized trials. Two trials treated patients with advanced NSCLC with either gemcitabine and cisplatin or the same chemotherapy drugs combined with two different doses of gefitinib or one dose of erlontinib (INTACT I and TALENT). The other two trials treated patients with advanced NSCLC with either paclitaxel and carboplatin or the same chemotherapy drugs combined with either one of two doses of gefitinib or a single dose of erlontinib (INTACT 2 or TRIBUTE respectively). The results of INTACT I and INTACT2 showed no significant difference in survival between those treated with conventional combination chemotherapy and those treated with the same chemotherapy plus gefitinib. The results of the TRIBUTE and TALENT studies showed their primary endpoints of improving overall survival were not met. The monoclonal antibody, bevacizumab, is being tested in an ongoing clinical trial. The trial will compare the outcome of patients with untreated advanced adenocarcinoma of the lung treated with paclitaxel plus carboplatin to those treated with the same chemotherapy drugs plus bevacizumab. The results are scheduled to be available in 2005-2006. Although the initial trials adding newly developed molecular targeted agents have not shown initial success when added to conventional combination chemotherapy, further clinical trials are needed to ultimately define their role in the treatment of non-small cell lung cancer. (C) 2004 Elsevier Ltd. All rights reserved.