With best supportive care alone, patients with metastatic non–smallcelllung cancer (NSCLC) have a median survival of 4 to 5 months anda 1-year survival rate of approximately 10%. Trials carried out in the1980s and 1990s comparing chemotherapy to best supportive care reportedvariable efficacy results; however, a pivotal meta-analysis of thesedata indicated that cisplatin-based chemotherapy provided a survivalbenefit in advanced NSCLC. In the past decade newer agents such asgemcitabine (Gemzar), vinorelbine, paclitaxel, and docetaxel (Taxotere)have all demonstrated activity in NSCLC as single agents; consequentlythese agents have been combined with cisplatin or carboplatin. Randomizedphase III trials comparing these “newer” platin-based doubletshave failed to identify an optimal platinum-based doublet therapyregimen. Though it is clear that chemotherapy is an appropriate treatmentfor many patients with lung cancer, there a sense in which the useof traditional chemotherapeutic agents has reached a therapeutic plateau.Increased understanding of cancer biology has revealed numerouspotential therapeutic strategies, including targeting the epidermalgrowth factor receptor, protein kinase C, rexinoid receptors, and theangiogenesis pathway. The Eastern Cooperative Oncology Group studyE4599 comparing paclitaxel/carboplatin with/without bevacizumab isthe first phase III randomized trial to show a survival advantage withthe addition of a molecularly targeted agent to chemotherapy in thechemotherapy-naive patient population. Future studies will involve theevaluation of additional targeted agents plus chemotherapy as well aslooking at combinations of these targeted agents alone or with chemotherapy.
