Thalidomide treatment in recurrent glioblastoma patients

Malignant tumours are angiogenesis-dependent diseases: the formation of new blood vessels is considered a crucial process for tumour growth and spreading. Thalidomide has been shown to inhibit angiogenesis induced by basic fibroblast growth factor and to decrease in vitro endothelial cell proliferation. For this property the drug is under investigation as an antitumour agent, although its mechanism of action as an agiogenesis inhibitor has not been established. To evaluate the safety and potential effectiveness of thalidomide, we conducted a pilot study on 22 patients (14 M and 8 F) with recurrent glioblastoma multiforme, already treated by chemotherapy with a KPS ≥ 60. Serial serum or blood samples were obtained in the patients and in 11 healthy controls to analyse possible variations in TNF-α, interleukin-12, soluble thrombomodulin and metalloproteinase 9, and VEGF and bFGF, factors involved in different phases of angiogenesis. Eleven patients died within two months from treatment onset. Eleven patients responded: 7 achieved stable disease and 4 partial response lasting from 2 to 5 months. In the last 4 patients CT scans after 2 months of treatment showed a shrinking of the tumour-enhancing area. All patients could tolerate the drug. No significat variations in soluble thrombomodulin and IL 12 were detected, while a decrease in TNFα, bFGF, VEGF and MMP-9 levels occurred during thalidomide treatment. Acccording to our results, the drug should be considered worthy of further investigation in the treatment of high-grade gliomas.