Weekly bolus topotecan as first-line therapy for extensive stage small cell lung cancer in patients who are elderly, poor performance status, or have severe coexistent illness: A Minnie Pearl Cancer Research Network phase II trial

Abstract

7275 Background: Topotecan given intravenously for 5 consecutive days every 3 weeks is standard second-line therapy for patients (pts) with relapsed small cell lung cancer (SCLC) and ovarian cancer. Weekly bolus topotecan produces significantly less toxicity than the 5 day schedule, and appears as active as the standard schedule in pts with relapsed ovarian cancer. Methods: This ongoing phase II study was designed to evaluate the toxicity and response rate of weekly bolus topotecan in pts with previously untreated extensive stage SCLC who were elderly (> 65 years), poor performance status (PS), or had 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 evaluable. Results: Seventeen pts of the required 40 pts have thus far been enrolled; 12 men, 5 women, ages 64–81 (median 71); PS 0=1, 1=4, 2=12). Thirteen pts are evaluable for response. Two pts have had partial responses (15%); 6 pts stable tumor (45%). Grade 3/4 neutropenia has been seen in 4 of 17 pts (24%), but no grade 3/4 thrombocytopenia was observed. Grade 2 fatigue was observed in 10 pts (56%) and grade 3 fatigue in 6 pts (35%). A total of 107 weeks of therapy have been administered. There were 15 weeks of treatment delay and 8% required dose reductions. Conclusions: Weekly bolus topotecan appears to have modest activity and is well tolerated in this poor prognostic group of pts with previously untreated extensive stage SCLC. We expect to evaluate 15 additional pts soon. Severe myelosuppression is seen less often than expected compared to the standard 5 day schedule of topotecan. Fatigue is an important toxicity and may be reduced by planned rest weeks. Studies of weekly topotecan in combination with other active cytotoxic agents should be considered in pts with extensive stage SCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline