Topotecan as first-line therapy for small cell lung cancer

Although current treatments for small-cell lung cancer (SCLC) yield objective response rates exceeding 50%, most patients relapse. Hence, research into the identification of novel agents and combinations that may improve therapy is ongoing. Topotecan, an established treatment for patients with recurrent SCLC, is being investigated as first-line therapy for SCLC because of its novel mechanism of action, non-cumulative toxicity and in vitro synergy with other active agents. Several phase II studies of doublet and triplet combination therapy with other agents, including paclitaxel, cisplatin, carboplatin and etoposide, have reported promising results for first-line treatment of SCLC. For example, in combination with paclitaxel, complete and overall responses were 3-67% and 45-100%, respectively, in extensive-stage disease. Furthermore, two studies of the triplet combination of topotecan with paclitaxel plus carboplatin yielded impressive complete response rates of 37-51% in limited-stage SCLC. The most frequent adverse events associated with topotecan-based regimens have been reported as neutropenia and thrombocytopenia so growth factor support is often incorporated into treatments. Several ongoing phase III studies will help to clarify the role of topotecan in the first-line treatment of SCLC.