Treatment > Antiangiogenesis · Thalidomide

Meeting Abstract

A phase II trial of the anti-angiogenic agent, thalidomide, in patients with recurrent high-grade gliomas

HA Fine, JS Loeffler, A Kyritsis, P Wen, PM Black, VA Levin, S Graham, WKA Yung

Thalidomide was initially introduced into the clinic as a sedative, but was quickly removed when its teratogenic effects were discovered. 
Recently, it has been demonstrated that thalidomide has potent anti-angiogenic activity in vivo, a property, that may be related to its mechanism of teratogenesis. 
Secondary to excellent oral bioavailability and minimal side effects, thalidomide is a promising anti-angiogenic agent for long-term therapy in patients with vascular tumors. 
We, therefore, conducted a phase II trial of thalidomide, administered as a daily 1200 mg dose, in patients with recurrent high grade astrocytomas and mixed gliomas. 
To date 32 patients have been accrued, of whom all are evaluable for toxicity and 10 of whom are evaluable for response. Major toxicities clearly related to the drug were extreme somnolence (3 patients), and a drug rash (2 patients). 
Other adverse events included seizures (5 patients, 2 of whom had no prior history of seizures), deep vein thrombosis, and unexplained fever (1 patient each). 
Minimal radiographic responses were seen in 2 of the first 10 evaluable patients, one of whom has remained on thalidomide for more than 7 months since her tumor recurrence. 
Extensive thalidomide pharmacokinetics and serial assays for basic fibroblastic growth factor, a biologic marker of angiogenesis, have been evaluated in all patients, and the results of these studies, along with an update on the total cohort of 35 patients, will be presented at the time of the meeting. 
In summary, thalidomide is one of the first anti-angiogenic agents to be studied in a prospective trial in patients with recurrent malignant gliomas and preliminary results suggest that it is well tolerated and appears to have some biologic activity at the currently utilized dose schedule.

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