Phase II study of a 3-day schedule with topotecan and cisplatin in patients with previously untreated small cell lung cancer and extensive disease.

INTRODUCTION: Treatment with a topoisomerase I inhibitor in combination with a platinum results in superior or equal survival compared with etoposide-based treatment in extensive disease small cell lung cancer (SCLC). Five-day topotecan is inconvenient and therefore shorter schedules of topotecan and cisplatin are needed. The aim of this phase II study was to establish the response rate and response duration in chemo-naive patients with SCLC receiving a 3-day topotecan and cisplatin schedule. METHODS: Simons optimal two-stage design was used. Patients with previously untreated extensive disease SCLC, adequate organ functions and performance status less than 3 were eligible. Topotecan (2.0 mg/m, intravenously) was administered on days 1 to 3 with cisplatin (50 mg/m, intravenously) on day 3 every 3 weeks for a total of six cycles. RESULTS: Forty-three patients received 219 cycles of chemotherapy. Median age was 59 (range 44-74), 79% had performance status 0 or 1. Thirty-one patients completed all six cycles. Grade 3/4 anemia, neutrocytopenia, and thrombocytopenia were recorded in 9.5%, 66.7%, and 21.4% of patients, respectively. Fourteen percent of patients experienced neutropenic fever. No episodes of fatal sepsis occurred. Non-hematologic toxicity was mild and manageable. Overall and complete response rates were 72.1% and 9.3%, respectively. The median overall survival and response duration were 10.3 months (95% confidence interval: 8.6-12.0) and 7.0 months (95% confidence interval: 6.3-7.7), respectively. CONCLUSION: Three-day topotecan with cisplatin on day 3 is active and safe in extensive disease SCLC. An ongoing phase III randomized trial compares this combination to standard treatment.

Topotecan and cisplatin in combination with concurrent twice-daily chemoradiation in limited disease small cell lung cancer-a Danish Oncological Lung Cancer Group (DOLG) phase II trial.

INTRODUCTION: The longest survival time reported in randomised trials of limited disease (LD) SCLC has been achieved with early twice-daily concurrent chemoradiation. Topotecan is active in recurrent SCLC and in extensive disease as first line treatment. AIM: To incorporate and assess the effect of topotecan with concurrent twice-daily radiochemotherapy in LD SCLC. PATIENT AND METHODS: Multicentre phase II study of three cycles of regimen A (topotecan i.v., 1.5mg/m(2), day 1-5; cisplatin 50mg/m(2), day 1) and three cycles of regimen B (etoposide i.v., 120mg/m(2), day 1-3; carboplatin, AUC=5, day 1; vincristine, 1.3mg/m(2), day 1) given in the following sequence: A-B-B-A-B-A every 21 days. Twice-daily radiotherapy (1.5Gyx30, 10fr/wk, 45Gy) was delivered concurrently with the first cycle B. Prophylactic cranial irradiation was offered to patients (pts) in complete remission. Eligible were pts with LD SCLC with no prior treatment for SCLC, adequate organ functions, and WHO performance status (PS) < or =2. Pts older than 64 years with PS=2 and LDH>two times the upper limit were excluded. RESULT: Fourty-five pts were included in four centres. Five patients did not meet the inclusion criteria. The median age of the eligible pts was 60 years, range 43-75. PS was < or =1 in 90% of pts. Non-haematological toxicity was mild except grade 3 esophagitis, which was observed in 26.5% of pts. One pt developed an esophageal stricture. Grade 3/4 leucopenia and thrombocytopenia were observed in 82.5% and 75.0 of pts, respectively. One patient died due to neutropenic sepsis. The overall response rate was 77.5% with 30.0% achieving a complete response. Median progression-free survival was 11.8 months (95% CI: 1.3-22.2). Median overall survival was 22.9 months (95% CI: 13.4-31.5) and 5-year survival was 21%. CONCLUSION: The combination of topotecan and cisplatin with concurrent twice-daily chemoradiation results in long-term survivors. As expected the incidence of severe esophagitis is high.