Topotecan in the Treatment of Recurrent Small Cell Lung Cancer: An Update

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 typically high, but short lived. The outlook for patients with recurrent SCLC is poor. A variety of single- and multi-agent chemotherapy regimens have met with limited success in patients with recurrent SCLC, and survival is generally measured in weeks. Until recently, further chemotherapy was not widely considered appropriate for patients with relapsed SCLC. The choice of chemotherapy at relapse is dependent on many factors, including type of and response to first-line therapy, the treatment-free interval, and the patient's performance status. Intravenous topotecan (Hycamtin; GlaxoSmithKline; Philadelphia, PA) has provided oncologists and patients in many countries with an effective and tolerable therapeutic option for recurrent SCLC. The clinical profile of topotecan was established in several phase II studies and confirmed in a randomized, phase III trial versus cyclophosphamide, doxorubicin (Adriamycin; Bedford Laboratories; Bedford, OH), and vincristine (Oncovin; Eli Lilly and Company; Indianapolis, IN)--CAV. In those studies, topotecan exhibited antitumor activity in both chemosensitive and refractory disease. Further, topotecan therapy is associated with significant symptom palliation in this patient population. Because the toxicity profile of topotecan is predictable, generally manageable, and noncumulative, the agent also has potential utility in patients with a poor prognosis and/or a poor performance status. Alternative dosing regimens (lower dose, weekly) and the introduction of an oral formulation may expand the use of topotecan as a single agent and in combination therapy in the second- and first-line treatment of this disease.