Phase II study of Thalidomide in the treatment of recurrent glioblastoma multiforme

Treatment options and prognosis remains poor for patients with recurrent gl ioblastoma multiforme. These tumors are highly vascularised and over expres s angiogenic factors such as vascular endothelial growth factor and may pot entially be responsive to antiangiogenic therapies. We present the results of a phase II trial of Thalidomide, an antiangiogenic agent, in the treatme nt of recurrent glioblastoma multiforme. Patients were treated with 100 mg/ day of Thalidomide, increased at weekly intervals by 100 mg to a maximum to lerated dose of 500 mg/d. Forty-two patients were enrolled, with 38 patients being assessable for res ponse and 39 for toxicity. Two patients (5%) achieved a partial response an d 16 (42%) had stable disease. The median survival was 31 weeks and the 1-y ear survival was 35%. Patients who had a partial response or stable disease had either a stabilisation or improvement in quality of life scores or per formance status. Overall Thalidomide was well tolerated with no grade 4 tox icities and no treatment related deaths. The median maximum tolerated dose was 300 mg/day. The most common toxicity was fatigue to which patients deve loped tachyphylaxis. There was no correlation demonstrated with plasma vasc ular endothelial growth factor levels and response or survival. Thalidomide is a well-tolerated drug that may have some activity in the tre atment of recurrent glioblastoma. Optimum dosing with antiangiogenic agents is currently under investigation. Chronic low dose therapy may be required to see conventional responses or improvements in time to progression. The dose required to achieve optimal biological impact may be better defined on ce we have established reliable surrogate endpoints.