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However, single-agent trials with antiangiogenic agents against malignancies have shown disappointing activity or unacceptable toxicity.
Preclinical data suggest that certain antiangiogenic agents can increase vascular perfusion in tumors by decreasing edema and reducing interstitial pressure.
This can potentially improve the delivery of concurrently used cytotoxic agents to the tumor, resulting in improved efficacy.
Consequently, strategies that combine cytotoxic and antiangiogenic approaches to target the tumor in two distinct ways critical to its biology could maximize the potential of these agents.
The combination of irinotecan, a cytotoxic agent, and thalidomide, an antiangiogenic agent, shows promising activity against recurrent GBM in patients not receiving EIACs and warrants further study.
The results also provide support for similar strategies using combination therapies with newer targeted antiangiogenic agents to generate effective therapies against malignant gliomas.
Glioblastoma multiforme (GBM) is associated with significant morbidity and a disproportionately high rate of mortality.
For most patients with recurrent GBM, there is no approved standard of care, and these patients survive only a few months after tumor progression.New strategies that can selectively target the biology of tumors are clearly needed.Neoangiogenesis and proliferation are recognized features of recurrent GBM and are logical targets for therapy.This phase II study aimed at determining the efficacy and safety of irinotecan combined with thalidomide in adults with recurrent glioblastoma multiforme (GBM) not taking enzyme-inducing anticonvulsants (EIACs).Adult patients (≥18 years) with recurrent GBM with up to three relapses following surgery and radiation therapy were eligible for this trial.