BACKGROUND: Therapeutic options for patients with anaplastic gliomas (AGs) are 
limited despite better insights into glioma biology. The authors previously 
reported improved outcome in patients with recurrent glioblastoma treated with 
thalidomide and irinotecan compared with historical controls. Here, results of 
the AG arm of the study are reported, using this drug combination.
METHODS: Adults with recurrent AG previously treated with radiation therapy, 
with Karnofsky performance score ≥70, adequate organ function and not on 
enzyme-inducing anticonvulsants were enrolled. Treatment was in 6-week cycles 
with irinotecan at 125 mg/m(2) weekly for 4 weeks followed by 2 weeks off, and 
thalidomide at 100 mg daily increased to 400 mg/day as tolerated. The primary 
endpoint was progression-free survival rate at 6 months (PFS-6), and the 
secondary endpoints were overall survival (OS) and response rate (RR).
RESULTS: In 39 eligible patients, PFS-6 for the intent-to-treat population was 
36% (95% confidence interval [CI] = 21%, 53%), median PFS was 13 weeks (95% CI = 
6%, 28%) and RR was 10%(95% CI = 3%, 24%). Radiological findings included 2 
complete and 2 partial responses and 17 stable disease. Median OS from study 
registration was 62 weeks, (95% CI = 51, 144). Treatment-related toxicities 
(grade 3 or higher) included neutropenia, diarrhea, nausea, and fatigue; 6 
patients experienced venous thromboembolism. Four deaths were attributable to 
treatment-related toxicities: 1 from pulmonary embolism, 2 from colitis, and 1 
from urosepsis.
CONCLUSIONS: The combination of thalidomide and irinotecan did not achieve 
sufficient efficacy to warrant further investigation against AG, although a 
subset of patients experienced prolonged PFS/OS. A trial of the more potent 
thalidomide analogue, lenalidomide, in combination with irinotecan against AG is 
currently ongoing.