Topotecan—Single agent activity in a weekly intravenous (IV) schedule for first-line therapy in poor prognosis extensive stage small cell lung cancer (SCLC): A Minnie Pearl Cancer Research Network phase II trial

Abstract

17000 Background: Topotecan IV weekly produces significantly less myelotoxicity than the standard 5-day IV schedule and appears as active in patients (pts) with relapsed ovarian cancer. Topotecan 5-day IV schedule is the standard for second-line therapy for pts with sensitive relapse SCLC. Methods: The primary endpoints were to determine the response rate and toxicity of weekly topotecan IV in pts with previously untreated extensive stage SCLC who were elderly, with poor performance status (PS), or severe coexistent medical illness. 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 eligible. Results: 39 pts were enrolled: 21 men, 18 women; age range 60–90 (median 71); PS 0 = 2, 1 = 18, 2 = 19). 31 pts were evaluable by WHO criteria for response. 4 pts had partial responses (13%, 95% CI 4%-30%); 20 pts (65%) had stable disease (4 had minor responses with tumor shrinkage of 29%, 19%, 12%, and 5%); 7 pts had progressive disease (22%). 15 pts completed 12 weeks of therapy. Grade 3/4 neutropenia/thrombocytopenia was seen in 11 pts and 3 pts; grade 3 infection 4 pts; grade 3/4 fatigue 12 pts. A total of 225 weeks of therapy was administered with 32 weeks of treatment delay and 10% required dose reduction. There were no treatment-related deaths. The median and 1-year survival of PR/stable pts were 5.6 months and 24%. Conclusions: Topotecan IV weekly has activity and was relatively well tolerated as first-line therapy in this very poor prognostic group of pts with extensive stage SCLC. The therapeutic index is improved with weekly topotecan IV schedule in contrast to the 5-day IV schedule. Additional study of weekly topotecan in combination with other agents in SCLC is warranted. [Table: see text]

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

“…Data on weekly scheduling of topotecan in SCLC has been limited to small phase II studies at our center 17,18 and by Shah et al 25 In each of these trials, weekly topotecan (4 mg/m 2 ) could be safely administered, but response efficacy was low. Indeed, this led to a subsequent phase II trial at our center looking at a higher dose of weekly topotecan (6 mg/m 2 weekly for 6 of 8 weeks).…”

“…[12][13][14][15][16] Our group has studied weekly scheduling in the patients with relapsed SCLC and as first-line SCLC therapy in poor performance status (PS) patients. 17,18 Weekly dosing was well tolerated and associated with relatively low severe hematologic toxicity.…”