Weekly bolus topotecan as secondary therapy in extensive stage small cell lung cancer: A Minnie Pearl Cancer Research Network phase II trial

Abstract

7278 Background: Topotecan given intravenously for 5 consecutive days every 3 weeks is standard secondary therapy for patients with relapsed small cell lung cancer, but the average objective response rate from multiple studies is less than 20%. Weekly bolus topotecan appears to be active in relapsed ovarian cancer and is associated with significantly less myelosuppression than the 5 day schedule. Methods: A phase II trial as secondary therapy for relapsed small cell carcinoma is currently ongoing. Topotecan 4mg/m2 IV over 30 minutes for 12 consecutive weeks was planned. Doses were held or reduced based on toxicity. Patients were evaluated for response after 4 weeks; at least 3 weeks of therapy were required to be evaluable for response. Results: Thirty evaluable patients of the required 100 patients have been enrolled; 19 with sensitive relapse and 11 with resistant relapse. None of the 11 patients with resistant relapse have had partial responses; 3 patients had stable disease and 8 patients progressive disease. One of 19 patients (5%) with sensitive relapse had a partial response, 7 patients had stable disease and 11 patients progressive disease. A total of 213 weeks of therapy have been administered. There were 25 weeks of treatment delays and 8.5% dose modifications. Grade 3/4 toxicities: neutropenia (17.5%); thrombocytopenia (5%); fatigue (17.5%). Grade 2 fatigue was seen in 42.5%. There were no treatment-related deaths. Conclusions: Weekly bolus topotecan produces less severe myelosuppression than seen with the standard 5 day schedule, and fatigue is an important toxicity which might be reduced by planned rest weeks. This is an ongoing trial, but weekly topotecan appears to have minimal activity in this setting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline