Phase II study of thalidomide and daily cyclophosphamide for adults with malignant glioma.

1554 Background: We performed a phase II study to determine the activity and toxicity of thalidomide plus daily cyclophosphamide in patients with recurrent anaplastic astrocytomas (AA) and anaplastic oligodendrogliomas (AO). METHODS: Eligibility: adult patients with AA or AO in first relapse with measurable disease; interval of at least 3 weeks between surgical resection or 6 weeks between radiotherapy or chemotherapy; Karnofsky ≥ 60%; negative pregnancy test; and adequate marrow, renal, and hepatic function. Thalidomide was begun at 100 mg at bedtime and increased by 100 mg weekly to a maximum dose of 400 mg. Cyclophosphamide was administered at 100 mg daily. Responses were assessed every eight weeks and patients remained on study for up to one year or until disease progression or unacceptable toxicity. RESULTS: To date, 11 patients with recurrent AA (n = 10) or AO (n=1) have been enrolled (planned accrual=30). Median age is 38 years (range: 27 to 51). All patients received prior radiation therapy and chemotherapy (median: 2, range: 1 to 3). Grade 3 or greater toxicities included neutropenia (grade 3, n=3; grade 4, n=2), and hyponatremia (grade 3, n=1). Responses include one complete and one partial, both of these patients completed one year of treatment and remain off therapy with no evidence of disease progression. One patient achieved stable disease and is in the 21(st) week of therapy. Five patients progressed after cycle one. Two patients are too early for evaluation and one patient died of intratumoral hemorrhage after six days on protocol. CONCLUSIONS: Thalidomide plus daily cyclophosphamide demonstrates encouraging activity and is well tolerated among patients with recurrent AA or AO. [Table: see text].

Duke Scholars

Author Henry Seth Friedman Neurosurgery, Neuro-Oncology