Background: Temozolomide (TMZ; Temodal™/Temodar™) recently showed promising results in the first-line therapy of glioblastoma (Stupp R, 2004). Pegylated liposomal doxorubicin (PEG-Dox; Caelyx™/Doxil™) was successfully evaluated in patients with recurrent high-grade glioma (Fabel K, 2001; Hau P, 2002). Therefore, a combination of both agents seems promising. Here, we update data on a pilot phase II-trial using this regimen. Methods: We initiated a combination regimen consisting of TMZ and PEG-Dox in the first-line therapy of patients with glioblastoma. TMZ is given during standard radiotherapy (initiation) and on days 1-5 in 28 days starting 4 weeks after completion of radiotherapy (maintainance). PEG-Dox is given as a short-time infusion in a dose-escalation regimen once prior to radiotherapy (initiation) and on days 1 and 15 starting 4 weeks after completion of radiotherapy (maintainance). PEG-Dox is escalated for 5 mg/m2 in groups of three patients with a highest dose of 20 mg/m2 (group 4). Primary end point is dose limiting toxicity (DLT) in the toxicity phase and time to progression in the efficacy phase. Results: In the first treatment group (5 mg/m2 of PEG-Dox), one out of 7 evaluable patients had a dose limiting toxicity (DLT). In the second, third and fourth treatment groups using 10, 15 and 20 mg/m2 of PEG-Dox, the regimen was tolerated without DLT. Concerning efficacy in the “treated-patients” analysis of 17 patients treated so far, 1 had a partial response in MRI, and 12 patients had tumor stabilization 4 weeks after conclusion of radiotherapy. As no DLT was observed in dose group 4, the efficacy phase of the study will be performed with 20 mg/m2 of PEG-Dox. Accrual has started Nov 2004. Discussion: Considering the results of the dose escalation phase of this study, the regimen is feasible, tolerable, and able to induce objective responses and stabilizations in patients with glioblastoma using the standard dose of TMZ and 5 to 20 mg/m2 of PEG-Dox.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]