Advances in the therapy of high-grade glioma at relapse: pegylated liposomal doxorubicin

Abstract

Approaches to improve the prognosis of patients with high-grade glioma, which is still grim despite combined therapy and major advances in the development of new drugs, are highly important. Chemotherapeutic agents have not consistently produced favorable results in the relapse setting so far, with tumor responses reported in a minority of cases. Among them, doxorubicin has not shown significant efficacy, despite being one of the most effective substances in vitro and in animal models. Nevertheless, encapsulation of doxorubicin using polyethylene-glycol significantly improves penetration across the blood–brain barrier. Moreover, recent clinical trials in other entities have demonstrated that similar clinical responses can be achieved using approximately half of the dose of polyethylene-glycol-liposomes compared with conventional liposomes. Considering these facts, polyethylene-glycol-liposomal doxorubicin with and without tamoxifen was evaluated within two sequential Phase II trials performed at our institution. Polyethylene-glycol-liposomal doxorubicin (Caelyx™) was efficient in a reasonable number of patients with equivalent results in comparison with other successful Phase II studies. This article will discuss the literature and our own results on polyethylene-glycol-liposomal doxorubicin, with a special focus on toxicity and efficacy data raised in clinical trials on patients with high-grade glioma.

• anthracycline
• Caelyx
• doxorubicin
• high-grade glioma
• pegylated liposomal
• relapse