Imatinib plus hydroxyurea in pretreated nonprogressive glioblastoma (GBM): Long-term follow up of a single-center phase II study.

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e13004 Background: GBM is malignant brain tumour with a median survival of 15.6 months. Dysregulated signalling of platelet derived growth factor receptors is suggested to play a role in pathogenesis. The combination of imatinib (I) plus hydroxyurea (HU) is known to be well tolerated and to show moderate efficacy in patients (pts) with recurrent GBM. Despite the aggressive course of GBM once starting progression, short periods of disease stabilisation after primary treatment or effective treatment of relapse can be observed. This Phase II study was initiated to analyse the efficacy of I plus HU as maintenance treatment (MT) in GBM pts. Methods: From December 2003 up to June 2005 30 pts were included. No enzyme-inducing anticonvulsive drugs were allowed. I (600 mg/day) and HU (1000 mg/day) were given as a continuous treatment. Blood cell counts were taken weekly and magnetic resonance imaging every 6 weeks. Primary endpoint (PE) was 6 and 12 months progression free survival (PFS), secondary endpoints (SE) were 5 years PFS and overall survival (OS). Results: All pts were eligible for PE and SE. 25 pts were male, 5 pts female, median age was 44 years (32 to 71). All pts had prior irradiation, 21 pts had prior temozolomide (T) containing therapy and 9 pts non-temozolomide containing therapy. 8 pts had none, 17 pts one and 5 pts two prior relapses. 25 pts had measurable disease, 4 of these pts achieved a partial response (PR), there was no complete remission, 5 pts had no evidence of disease. Median follow up is 90 months. Hematotoxicity grade 2 and 3 occurred in 11 out of 30 pts and required dose reduction of HU in 8 pts, dose reduction of I in 1 patient and G-CSF in 8 pts. PFS rate at 6, 12, 24 and 60 months were 60% (18/30), 40% (12/30), 17% (5/30) and 17% (5/30 ) respectively, OS rate at 6, 12, 24 and 60 months were 90% (27/30), 67% (20/30), 37% (11/30) and 17% (5/30). 4 pts are still alive without progression. Conclusions: Although I and HU did not demonstrate relevant efficacy in GBM and never reached admission status the reported study indicates impressive long-term survival data for I and HU as a continuous oral MT. Further studies should analyse more effective drugs like temozolomide as MT (proof of principle). Clinical trial information: STI571DE21.