New Advances in the Second-Line Treatment of Small Cell Lung Cancer

Lungcanceristheleadingcauseofcancer-relateddeathin the U.K., with small cell histology accounting for 15%– 20% of cases. Small cell lung cancer (SCLC) is initially a chemosensitive disease, but relapse is common, and in this group of patients it remains a rapidly lethal disease with a particularlypoorprognosis.Thechoiceofsecond-linechemotherapy for patients with relapsed SCLC has been an area of difficulty for oncologists, and until recently there was no randomized evidence for its use over best supportive care (BSC). Topotecan is currently the only drug licensed in Europe and the U.S. for this indication, having beenshowninaphaseIIItrialtoleadtolongeroverallsurvival and better quality of life than with BSC. In this article, we review the current evidence for the use of secondline cytotoxic therapy and also the emerging role of novel agents and targeted therapies in this setting. In particular, we explore the role of the Bcl-2 protein family, which are key regulators of mitochondrial apoptosis and are implicated in resistance to anticancer therapies. SCLC overexpresses antiapoptotic members of the Bcl-2 family in 80% of cases. Several Bcl-2 inhibitors, including obatoclax,arecurrentlyenteringclinicaltrialsinSCLCandare an exciting area of drug development in the relapsed setting. The Oncologist 2009;14:986–994