Topotecan has demonstrated significant activity in the second-line treatment of small-cell lung cancer (SCLC), particularly in patients sensitive to prior chemotherapy regimens. A study involving 101 patients assessed the efficacy and toxicity of topotecan in previously treated SCLC patients, revealing promising response rates and manageable toxicity profiles.
Study Design and Patient Population
The study enrolled patients with measurable SCLC who had experienced disease progression following one first-line chemotherapy regimen. Patients were categorized into two groups: those who failed first-line treatment within three months of discontinuation (refractory group) and those who responded to first-line treatment but progressed more than three months after discontinuation (sensitive group). Topotecan was administered via a 30-minute daily infusion at a dose of 1.5 mg/m2 for five consecutive days, repeated every three weeks.
Efficacy Results
Of the 92 eligible patients assessable for response, the refractory group (n=47) showed an overall response rate of 6.4% (95% CI, 1.3% to 17.6%), comprising two partial responses (PRs) and one complete response (CR). In contrast, the sensitive group (n=45) exhibited a significantly higher overall response rate of 37.8% (95% CI, 23.8% to 53.5%), with 11 PRs and six CRs. The median duration of response was 7.6 months.
Median survival for all patients was 5.4 months. The refractory group had a median survival of 4.7 months, while the sensitive group showed a median survival of 6.9 months (P = .002). Responding patients had a median survival of 12.5 months.
Safety Profile
The primary toxicity observed was hematologic, with universal leukopenia. Grade III and IV neutropenia occurred in 28% and 46.8% of cycles, respectively, but was generally short-lived. Non-hematological toxicity was mild, with fatigue/malaise reported in 39.3% of cycles and transient elevation of liver enzymes in 17%.
Clinical Implications
These findings suggest that topotecan is an active agent in the treatment of SCLC, especially in patients sensitive to prior chemotherapy. The manageable toxicity profile supports the incorporation of topotecan into combination chemotherapy regimens for future SCLC treatment strategies. Further research is warranted to explore optimal combinations and sequencing strategies to maximize the benefits of topotecan in SCLC management.
