Thalidomide (Thalomid) has been demonstrated to be an antiangiogenic
agent with some activity in glioblastoma multiforme. This ongoing
study currently has 37 enrolled patients. Patients were started on a
dose of 100 mg/d of thalidomide. This was increased by 100 mg/d,
weekly, to a maximum dose of 500 mg/d, if tolerated. The mean age was
52 years (range: 2769 years). The male/female ratio was 19/18.
The mean dose tolerated was 300 mg, with a range of 200 to 500 mg/d.
Patients were stratified by such prognostic factors as debulking
surgery, previous response to treatment, age, and performance status.
Twenty-seven patients had documented glioblastoma multiforme at
initial diagnosis, while 10 were initially diagnosed as having lower
grade tumors and were confirmed to have glioblastoma multiforme at
recurrence. At initial diagnosis, 28 patients had debulking surgery.
All patients had received radiotherapy. Seventeen patients had
received prior chemotherapy.
Thirty-four patients were assessable for response: 5 (15%) patients
achieved a partial response and 11 (32%) achieved stable disease.
Eighteen patients had progressive disease. The median survival in
this group was 27 weeks. In all the patients in whom a partial
response or stable disease was achieved, there was either a
stabilization or reduction in the steroid dose. Assessment of quality
of life or Karnofsky performance status also showed improvement or
stabilization in the group of patients with partial response or
stable disease. Plasma vascular endothelial growth factor (VEGF)
levels were assessed in these patients. There was no correlation with
plasma VEGF levels and response or prognosis. Thalidomide was
well-tolerated with no grade 4 toxicities. The most common toxicity
was fatigue. Skin rash occurred in four patients. Quantitative
sensory neural testing was performed on all patients, three of which
demonstrated deterioration and two of which had associated paresthesia.
CONCLUSION: Thalidomide is a well-tolerated antiangiogenic
agent with some biologic activity in recurrent glioblastoma