Clinical trial enrollment should be considered at all stages of treatment of SCLC. This review highlights the available treatment options in relapsed SCLC. In particular, we focus on prospective clinical trials demonstrating activity for the most commonly used agents in this setting. For relapse ≤ 6 months of initial therapy, sequential therapy with single agents is recommended. The incidence of small-cell lung cancer (SCLC) has steadily decreased in the United States, where it constitutes roughly 13% of all new lung cancer diagnoses.1 In contrast to non–small-cell lung cancer, SCLC represents the most aggressive form of lung cancer, with a rapid doubling time, tendency for early and widespread metastases, and high sensitivity to initial therapy followed by eventual resistance on disease recurrence.

The median overall survival (OS) approximates 20 months in limited-stage SCLC, with estimated 5-year survival rates of < 15%, whereas the median OS is approximately 8 to 12 months for extensive-stage SCLC, with 5-year survival rates of < 2%. A separate multicenter retrospective analysis included 120 patients who received third-line chemotherapy for relapsed SCLC from 2000 to 2010; rechallenge with platinum-based chemotherapy (57%) was the most common second-line regimen, followed by CAV (26%), enrollment in a clinical trial (17%), and topotecan (11%).

In conclusion, systemic therapy after first-line treatment failure remains an important component of the treatment paradigm for SCLC, given that most patients will experience relapse during the course of the disease.