Topotecan in the treatment of recurrent small-cell lung cancer

Abstract

Small cell lung cancer (SCLC) is an aggressive malignancy with a high propensity for early regional and distant metastasis. Response rates to first-line chemotherapy are high, but typically short-lived. Nearly all patients with extensive disease and most patients with limited disease will experience recurrent disease. The outcome of patients with recurrent SCLC is poor despite the use of second-line therapy. A number of single and multiagent chemotherapy regimens showed limited efficacy in patient with recurrent SCLC and overall survival is generally short (in the range of weeks). The choice of chemotherapy at relapse depends on many factors, including type of first-line chemotherapy and response, treatment- free interval and patient's performance status. Topotecan is a topoisomerase I inhibitor with established antitumor activity in recurrent SCLC. Topotecan has a predictable non-cumulative toxicity profile and is well tolerated, that makes this agent potentially useful in patients with poor performance status. Data suggests that topotecan penetrates the blood-brain barrier and might have activity in the treatment of SCLC patients with brain metastases. Topotecan has been shown to provide symptom improvement in recurrent SCLC, which is predominantly palliative setting. Furthermore, evidence suggests that second-line oral topotecan extends survival in patients with relapsed, resistant SCLC by a clinically and statistically significant margin and offers a better life quality. This article reviews the clinical utility of topotecan in recurrent SCLC.