Treatment > Antiangiogenesis · Carboplatin · Thalidomide

Meeting Abstract

Phase I/II Study of Carboplatin and Thalidomide in Recurrent Glioblastoma Multiforme

Jo Glass, Gruber Michael , Anit Nirenberg

Despite recent advances in the development of treatment modalities in patients with recurrent Glioblastoma Multiforme (GBM), prognosis remains poor. 
Thalidomide, a putative anti-angiogenesis agent, has been shown to have possible activity against GBM. 
We performed a phase I/II study of thalidomide in combination with carboplatin, an agent commonly used in recurrent GBM, to assess the safety and efficacy of this combination. 
As part of a phase I/II study of carboplatin and thalidomide for recurrent malignant glioma, we treated 71 patients with recurrent GBM. 
All patients received carboplatin at a dose calculated utilizing an AUC of 8 with the Calvert formula. 
Thalidomide was administered orally on a daily basis. 
An initial dose escalation (100 mg/sq m in 100 mg/sq m increments) was performed to determine the maximum tolerated dose (MTD) of thalidomide. 
Once MTD was determined, the remainder of patients were treated at that dose level. Six cycles of carboplatin were planned, and thalidomide was continued until recurrence. 
The MTD of thalidomide was determined to be 300 mg/sq m. 
At the MTD, 64 patients were assessable for toxicity and 46 were assessable for efficacy. 
33 patients had responses (5 PR, 28 SD) and 13 had progressive disease. 
Estimated median survival was 40 weeks. 
Median response duration was 24 weeks. 
Hematologic toxicity was most prominent in patients previously receiving nitrosurea and included grade 3/4 thrombocytopenia in 88 of 161 cycles, and grade 3/4 neutropenia in 37 of 161 cycles. 
Major non-hematological toxicities included constipation and drowsiness which were attributed to thalidomide. 
The combination of carboplatin and thalidomide is active in recurrent GBM. 
Additional studies will be performed to further determine the efficacy of this combination in recurrent and newly diagnosed.

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