A Phase II Trial of Carboplatin and Weekly Topotecan in the First-Line Treatment of Patients with Extensive Stage Small Cell Lung Cancer

Background Carboplatin and topotecan are commonly used in the treatment of small cell lung cancer (SCLC); however, there are no data for this combination in the first-line setting using weekly topotecan. In this multicenter, community-based phase II trial, we evaluated carboplatin and weekly topotecan in the previously untreated patients with extensive stage SCLC. Methods This trial was designed to achieve an objective response rate (ORR) of 70% (α = 0.05; β = 0.20); secondary aims were to assess time to progression, toxicity, and overall survival (OS). Patients with Eastern Cooperative Oncology Group performance status 0 to 1, measurable disease, and adequate organ function were eligible. Treatment: carboplatin area under the concentration–time curve=5 (intravenous) on day 1 and topotecan 4 mg/m 2 (intravenous) on days 1 and 8, every 21 days for up to six cycles, with restaging every 6 weeks (per RECIST). Results Between June 2006 and November 2008, 61 patients were enrolled. The median follow-up is 40 weeks (range 27–109 weeks). Patient characteristics were as follows: median age 67 years (range 40–84 years); male, 53%; and Eastern Cooperative Oncology Group performance status 0, 28%. Complete responses were seen in two patients and partial responses in 33 patients; ORR was 57% (95% confidence interval [CI] 44–70). Stable disease was seen in 12 patients (20%), and progressive disease was seen in two patients (3%). The median time to progression was 5.5 months (95% CI 4.0–6.3 months). The median OS was 8.5 months (95% CI 7.2–11.4 months). One-year OS was 29%. Grade 3/4 toxicity in >5%: neutropenia (66%), thrombocytopenia (48%), leukopenia (40%), anemia (30%), fatigue (13%), dehydration (8%), infection (8%), and pain (7%). Conclusions The ORR achieved with carboplatin and weekly topotecan was less than the anticipated rate of 70%; however, it was comparable with historical rates seen with other platinum doublets in the first-line extensive stage SCLC setting. This regimen was generally well tolerated, with myelosuppression as its primary toxicity.