Topotecan: Weekly intravenous (IV) schedule similar to standard 5-day IV schedule as second-line therapy for relapsed small cell lung cancer (SCLC)—A Minnie Pearl Cancer Research Network phase II trial

Abstract

7083 Background: Topotecan IV weekly produces significantly less myelotoxicity than the standard 5-day IV schedule and appears as active as the 5-day schedule in patients (pts) with relapsed ovarian cancer. Topotecan 5-day IV schedule is the standard for second-line therapy for sensitive relapse SCLC. Methods: The primary endpoints of this phase II trial were to determine the response rate and toxicity of topotecan IV weekly as second-line therapy in patients with sensitive relapse (SR) and resistant relapse (RR) SCLC. Topotecan 4mg/m2 IV over 30 minutes for 12 consecutive weeks was planned. Dose modifications were made based on toxicity. Pts were evaluated for response after 4 weeks; at least 3 weekly treatments were required to be evaluable. Results: A total of 103 pts (59 SR; 44 RR) were enrolled: 56 men, 48 women; age range 42–86 (median 65); performance status 0=18, 1=69, 2=16, 3=1. 47 pts with SR and 34 pts with RR were evaluable for response by WHO criteria. For SR, 3 pts had partial response (6.4%, 95% CI 1.3%-17.5%), 17 pts had stable disease (7 had minor responses with tumor shrinkage of 39%, 27%, 21%, 20%, 20%, 7%, and 3%, respectively). Using RECIST criteria 5 pts had PR (13%, 95% CI 6%-25%). For RR, 1 pt had a CR (3%, 95% CI 0.1%-15.3%), 6 pts had stable disease (2 had minor responses with 36%, 5% tumor shrinkage). Grade 3/4 neutropenia/thrombocytopenia was seen in 17 and 22pts, grade 3 infection 6 pts; grade 3/4 fatigue 16 pts. There was 1 treatment-related death. Median and 1-year survival for all patients was 4.5 months (SR = 5.6 months; RR 3.2 months, p = 0.05) and 19% (SR = 22%; RR = 10%). There was no difference in survival for PR versus stable pts, and PR/stable had 1-year survival of 46% compared to PD of 9% (p < 0.0001). Conclusions: Topotecan IV weekly has similar activity to the standard 5-day IV schedule in SR SCLC, and considerably less myelotoxicity. These data support the weekly schedule for standard therapy of SR SCLC, and further study of weekly topotecan as a component of combination therapy for SCLC. [Table: see text]