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

Area of Science:

• Neuro-oncology
• Clinical pharmacology
• Cancer treatment research

Background:

• Recurrent glioblastoma (GBM) presents significant treatment challenges.
• Evaluating novel therapeutic combinations is crucial for improving patient outcomes.
• The role of enzyme-inducing anti-epileptic drugs (EIAEDs) in treatment efficacy requires investigation.

Purpose of the Study:

• To assess the efficacy and safety of imatinib mesylate plus hydroxyurea in recurrent GBM.
• To determine if EIAED use impacts the effectiveness of this combination therapy.
• To evaluate radiographic response, progression-free survival, and overall survival.

Main Methods:

• A clinical trial involving 231 patients with first-recurrent GBM across 21 institutions.
• Standardized dosing of hydroxyurea (500 mg twice daily) for all participants.
• Stratified imatinib mesylate dosing based on EIAED status (600 mg/day without EIAEDs, 500 mg twice daily with EIAEDs).

Main Results:

• The overall radiographic response rate was 3.4%.
• Progression-free survival at 6 months was 10.6%, with a median overall survival of 26.0 weeks.
• Adverse events, including fatigue, neutropenia, and thrombocytopenia, were manageable and did not differ significantly based on EIAED status.

Conclusions:

• Imatinib mesylate in combination with hydroxyurea is well-tolerated in recurrent GBM patients.
• This combination therapy did not demonstrate clinically meaningful anti-tumor activity.
• EIAED status did not appear to influence treatment outcomes in this study.