Phase II study of the combination of thalidomide and irinotecan in patients with recurrent anaplastic gliomas not on enzyme inducing anticonvulsants

Abstract

1564 Background: Patients with recurrent anaplastic glioma (AG) have few treatment options after initial alkylating agent therapy. In this study, the efficacy of thalidomide and irinotecan against recurrent AG was tested to assess if synergistic activity of cytotoxic and antiangiogenic agents could affect clinical outcome. Methods: Patients with recurrent AG with a KPS≥70 not on enzyme inducing anticonvulsants and with fewer than three relapses after radiation therapy and chemotherapies were eligible; the total planned enrollment is 39 patients. Irinotecan is administered at 125 mg/m2 weekly for 4 weeks followed by 2 weeks rest; thalidomide is initiated at 100 mg daily and escalated weekly up to 400 mg daily. Warfarin (1 mg) is given for prevention of venous thromboembolism (VTE). Patients undergo clinical and radiologic evaluations every 6-weeks. The primary endpoint is progression free survival at 6 months (PFS-6). To determine possible radiologic correlates to treatment effects, DCE- MR perfusion-imaging studies are obtained at baseline and subsequent follow up visits. Results: 17 are evaluable for response; the remainder were inevaluable. All evaluable patients had previously failed temozolomide and 9 had also failed nitrosourea therapy. The median age is 44 yrs and median KPS is 90. Four patients are alive and progression free at 6-months whereas 9 have progressed; the median progression free survival is 23 weeks and the PFS-6 is 34%. The best response was a CR in one patient, PR in 2 and stable disease in 9. Two patients have died of unspecified causes probably related to treatment. Median overall survival has not been reached; the 12-month and 18 month survivals by Kaplan Meier analysis are 73% and 26% respectively. Grade 3 and 4 toxicities included fatigue (29%), leukopenia (29%), nausea/vomitting (24%), and diarrhea (18%) requiring dose reductions. Two patients had VTE. Conclusions: The preliminary results of this ongoing study suggest that the combination of irinotecan and thalidomide has activity in patients with recurrent anaplastic gliomas; the ongoing assessment of this combination in patients with AG will more definitively define whether the combination can be an effective second line therapy for this population. [Table: see text]