Anne[a]
ASCO 2005 Abstract No: 1524
Phase II trial of Thalidomide in combination with Irinotecan in adults with recurrent glioblastoma multiforme
V. K. Puduvalli, P. Giglio, M. D. Groves, K. R. Hess, E. Jackson, S. Mahankali, M. Gilbert, V. A. Levin, C. Conrad, S. Hsu, W. Yung
Background:
Rationally designed combination chemotherapy can potentially improve the prognosis of patients with recurrent GBM. In this study, the efficacy of thalidomide and irinotecan against recurrent GBM was tested to assess if synergistic activity of cytotoxic and antiangiogenic agents could affect clinical outcome.
Methods:
In this ongoing phase II study, patients with recurrent GBM with a KPS≥70 and less than three relapses after radiation therapy and chemotherapies are eligible for entry; the total planned enrollment is 32 patients. Patients are placed on low dose daily warfarin (1 mg) for prevention of thrombosis. Non-enzyme-inducing anticonvulsants are mandated for those needing anti-seizure therapy. 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. 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:
Of the 26 evaluable patients enrolled to date, 24 have adequate follow up, the majority of whom have failed temozolomide or nitrosourea therapy. Median age is 48 years and median KPS is 90. Five patients are alive and progression free at 6-months whereas 16 have progressed with a median TTP of 14 weeks (95% CI: 11, Not Reached). The PFS-6 is 28% (13%, 60%). The best response was a PR in one patient and stable disease in 15. No treatment related deaths have been noted. There have been 3 deaths among the 26 patients with a 6-month survival by Kaplan Meier analysis being 82% (66%, 100%]). Grade 3 and 4 toxicities included fatigue, constipation, diarrhea, leukopenia, and typhilitis requiring dose reductions. Imaging data (DCE-MRI) and their correlation to clinical response will be presented.
Conclusions;
The results of this ongoing study suggest that the combination of irinotecan and thalidomide has promising activity in patients with recurrent glioblastomas following alkylator therapy and may warrant further assessment in this population