Phase II Trial of Oral Topotecan and Intravenous Carboplatin With G-CSF Support in Previously Untreated Patients With Extensive Stage Small Cell Lung Cancer

Abstract

Objectives The objective of this study was to evaluate the response rate and toxicities of the combination of oral topotecan and carboplatin in patients with untreated extensive stage small cell lung cancer (ES-SCLC). Previous studies have suggested improved outcomes with a topoisomerase I inhibitor in combination with a platinum agent. Methods Twenty-six patients with previously untreated, ES-SCLC were evaluable in this phase II trial. All patients received oral topotecan 2.0 mg/m2 per day on days 1 through 5 and carboplatin at an area under curve of 5 on day 5. Treatment was repeated every 21 days up to a total of 6 cycles. All patients received G-CSF. Results There were no complete responses and 16 partial responses, for an overall response rate of 62% (95% CI: 41–80). Median time to progression was 6.0 months (95% CI: 4–8), with a median overall survival of 12 months (95% CI: 8–16). This study was closed to accrual early with 26 of a planned 39 patients enrolled because of grade 5 adverse events in 4 (15%) patients (3 neutropenic infections, 1 sudden cardiac death). Eighty-five percent of patients experienced grade 3 or higher hematologic events. The most common severe nonhematologic events included diarrhea, vomiting, dyspnea, hypoxia, and hypotension. Conclusions Although this drug regimen has activity as first-line therapy in ES-SCLC, it is associated with excessive hematologic toxicity, which occurred in spite of growth factor support. Despite promising survival estimates, this particular combination and dose level of oral topotecan and carboplatin cannot be recommended.

Impact of disease progression date determination on progression‐free survival estimates in advanced lung cancer

“…An initial analysis was performed on individual patient data from consecutive NCCTG phase 2 trials, including 10 NSCLC trials and 4 SCLC trials 14‐26. We subsequently validated the findings using individual patient data from SWOG phase 2 trials, including 4 NSCLC trials and 3 SCLC trials 27‐33.…”

Pharmacodynamics and pharmacokinetics of oral topotecan in patients with advanced solid tumours and impaired renal function

“…Intravenous topotecan in combination with cisplatin is indicated for patients with cervical cancer with recurrence after radiotherapy and for patients with stage IV‐B disease. Safety and efficacy of oral topotecan alone and in combination with other chemotherapeutic and anti‐angiogenic agents has been explored in various phase I and II trials. In phase II and III studies in SCLC patients, intravenous (1.5 mg m −2 day −1 ) and oral (2.3 mg m −2 day −1 ) topotecan regimens demonstrateD similar response rates .…”