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Lung Cancer

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

^aCentre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland; ^bNorthern Ireland Cancer Centre, Belfast, Northern Ireland

Key Words. Small cell lung cancer • Relapsed • Chemotherapy • BCL-2 • Apoptosis

Correspondence: Dean A. Fennell, M.D., Ph.D., Thoracic Oncology Research Group, Centre for Cancer Research & Cell Biology, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland. Telephone: 44-28-9097-2762; Fax: 44-28-9097-2755; e-mail: d.fennell{at}qub.ac.uk

Received February 15, 2009; accepted for publication September 6, 2009; first published online in THE ONCOLOGIST Express on October 9, 2009.

Disclosures: Jane L. Hurwitz: None; Francis McCoy: None; Paula Scullin: None; Dean A. Fennell: None.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors or independent peer reviewers.

Lung cancer is the leading cause of cancer-related death in 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 particularly poor prognosis. The choice of second-line chemotherapy 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 been shown in a phase III trial to lead to longer overall survival and better quality of life than with BSC. In this article, we review the current evidence for the use of second-line 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, are currently entering clinical trials in SCLC and are an exciting area of drug development in the relapsed setting.