PURPOSE: Little progress has been made in the treatment of adult high-grade 
gliomas over the last two decades, thus necessitating a search for novel 
therapeutic strategies. Malignant gliomas are vascular or angiogenic tumors, 
which leads to the supposition that angiogenesis inhibition may represent a 
potentially promising strategy in the treatment of these tumors. We present the 
results of a phase II trial of thalidomide, a putative inhibitor of 
angiogenesis, in the treatment of adults with previously irradiated, recurrent 
high-grade gliomas.
PATIENTS AND METHODS: Patients with a histologic diagnosis of anaplastic mixed 
glioma, anaplastic astrocytoma, or glioblastoma multiforme who had radiographic 
demonstration of tumor progression after standard external-beam radiotherapy 
with or without chemotherapy were eligible. Patients were initially treated with 
thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks until a 
final daily dose of 1,200 mg was achieved. Patients were evaluated every 8 weeks 
for response by both clinical and radiographic criteria.
RESULTS: A total of 39 patients were accrued, with 36 patients being assessable 
for both toxicity and response. Thalidomide was well tolerated, with 
constipation and sedation being the major toxicities. One patient developed a 
grade 2 peripheral neuropathy after treatment with thalidomide for nearly a 
year. There were two objective radiographic partial responses (6%), two minor 
responses (6%), and 12 patients with stable disease (33%). Eight patients were 
alive more than 1 year after starting thalidomide, although almost all with 
tumor progression. Changes in serum levels of basic fibroblastic growth factor 
(bFGF) were correlated with time to tumor progression and overall survival.
CONCLUSION: Thalidomide is a generally well-tolerated drug that may have 
antitumor activity in a minority of patients with recurrent high-grade gliomas. 
Future studies will better define the usefulness of thalidomide in newly 
diagnosed patients with malignant gliomas and in combination with radiotherapy 
and chemotherapy. Additionally, studies will be needed to confirm the potential 
utility of changes in serum bFGF as a marker of antiangiogenic activity and/or 
glioma growth.