Topotecan is the only single-agent therapy approved by the U.S. Food and Drug Administration for the treatment of patients with recurrent small cell lung cancer (SCLC). Poor performance status (PS) at the time of relapse can hinder the ability of a patient to tolerate second-line chemotherapy. To investigate the feasibility of topotecan in the treatment of relapsed SCLC patients with PS 2 scores, we retrospectively analyzed data from five clinical trials that included 479 patients who were treated with single-agent topotecan at a dose of 1.5 mg/m2/day on days 1-5 of a 21-day course. Of these patients, 381 had a PS 0 or 1 and 98 had a PS 2. Topotecan was well tolerated by both patient groups. Hematologic toxicities were generally manageable, and neutropenia was noncumulative. With the exception of grade 3/4 anemia, the incidences of severe hematologic toxicities were not statistically different between the two groups. The nonhematologic toxicity profiles were also similar in the two patient groups. Treatment provided similar benefits, including antitumor response rates and symptom palliation, in PS 0/1 and PS 2 patients. As expected, the median overall survival time was shorter in patients with worse PS scores; the median overall survival times were 36.3 weeks, 25.4 weeks, and 16 weeks for PS 0, PS 1, and PS 2 patients, respectively. In conclusion, treatment with topotecan is feasible and well tolerated in patients with relapsed SCLC with suboptimal PS scores.