Pilot study of topotecan and thalidomide in patients with recurrent malignant gliomas

Abstract

e13019 Background: Adults with glioblastoma multiforme (GBM) treated with radiation and chemotherapy have median survival of less than 12 months from diagnosis. Topotecan is a topoisomerase-1 inhibitor with activity in brain tumors and very little nonhematologic toxicity. Continuous infusion has been shown to have decreased hematologic toxicity. Thalidomide has antiangiogenic and immnunomodulatory effects. The combination would offer a multitargeted approach with no overlapping toxicity. Methods: Single-center prospective phase II study of 10 patients (median age 50, range 38–70) with high-grade recurrent glioma treated at Rush University Medical Center between 2002 and 2006 following IRB approval. All patients had failed at least one standard therapy and received a combination of the two drugs: topotecan by continuous infusion for 21 days, every 28 days at 0.4 mg/m2/day through a permanent in-dwelling catheter and thalidomide with starting oral dose of 100 mg/day, escalated by 100 mg/day per week to maximum of 400 mg/day by day 28. Dose reductions were made for grade 3 and 4 hematologic or nonhematologic toxicities. All patients received coumadin 1 mg/day DVT/PE prophylaxis. Assessment of response was done every 8 weeks by MRI and MRS. Results: Median number of cycles of study drugs = 3; median time to progression = 4 months; median survival = 12 months; DVT/PE = 40% of patients with low-dose coumadin prophylaxis. Conclusions: The combination of topotecan and thalidomide is feasible and shows moderate activity. The study is limited by small size and thromboembolic complications likely related to thalidomide in 40% of patients. Low-dose coumadin prophylaxis was not adequate in preventing thrombosis. [Table: see text] No significant financial relationships to disclose.