Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

Abstract

Background: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs).

Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS).

Results: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%).

Conclusions: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

Figure 1

Representative example of c-KIT gene amplification detected by fluorescence in situ hybridisation (FISH). High-level amplification of c-KIT (red signals) detected along with two copies of chromosome 4 centromeres (green signals).

Figure 2

Kaplan–Meier plots of progression-free survival (A) and overall survival (B) for patients enrolled on H2201 and H2202 studies.