PURPOSE: Irinotecan is a cytotoxic agent with activity against gliomas. 
Thalidomide, an antiangiogenic agent, may play a role in the treatment of 
glioblastoma multiforme (GBM). To evaluate the combination of thalidomide and 
irinotecan, we conducted a phase II trial in adults with newly-diagnosed or 
recurrent GBM.
PATIENTS AND METHODS: Thalidomide was given at a dose of 100 mg/day, followed by 
dose escalation every 2 weeks by 100 mg/day to a target of 400 mg/day. 
Irinotecan was administered on day 1 of each 3 week cycle. Irinotecan dose was 
700 mg/m(2) for patients taking enzyme-inducing anticonvulsants and 350 mg/m(2) 
for all others. The primary endpoint was tumor response, assessed by MRI. 
Secondary endpoints were toxicity, progression-free survival, and overall 
survival.
RESULTS: Twenty-six patients with a median age of 55 years were enrolled, with 
fourteen evaluable for the primary outcome, although all patients were included 
for secondary endpoints. One patient (7%) exhibited a partial response after 
twelve cycles, and eleven patients (79%) had stable disease. The intention to 
treat group with recurrent disease included 16 patients who had a 6-month PFS of 
19% (95% CI: 4-46%) and with newly-diagnosed disease included 10 patients who 
had a 6-month PFS of 40% (95% CI: 12-74%). Gastrointestinal (GI) toxicity was 
mild, but six patients (23%) experienced a venous thromboembolic complication. 
Two patients had Grade 4 treatment-related serious adverse events that required 
hospitalization. There were no treatment-related deaths.
CONCLUSION: The combination of irinotecan and thalidomide has limited activity 
against GBM. Mild GI toxicity was observed, but venous thromboembolic 
complications were common.