Pegylated-liposomal doxorubicin and oral topotecan in eight children with relapsed high-grade malignant brain tumors

Background : The combination of topoisomerase I and II chemotherapeutic agents has shown promising preclinical synergistic effects in the treatment of high-grade malignant brain tumors such as high-grade gliomas and choroid plexus carcinomas. To confirm the effectiveness of this treatment combination and determine its possible toxicity, we conducted a retrospective review of the charts of children who received the therapy. Methods : Patients with relapsed malignant brain tumors who were given an individualized treatment of pegylated (PEG)-liposomal doxorubicin and topotecan were included in our study. PEG-liposomal doxorubicin was given intravenously at a dosage of 30–40 mg/m 2 over 4 h once every 4 weeks. Additionally, an intravenous formulation of topotecan was given orally twice daily and was increased on an individual basis from a starting dosage of 0.3 mg/m 2 per application to a total daily dosage of 0.6 mg/m 2 . Results : Eight patients were included. The main toxicity (NCI-CTC) after three cycles of the combination therapy was grade IV hematotoxicity ( n = 3); grade III hematotoxicity ( n = 2), grade III stomatitis ( n = 1), grade III infection ( n = 2), grade III diarrhea ( n = 1); and grade II dermatitis ( n = 1). In four patients, stable disease was achieved for 9, 23, more than 24, and more than 48 weeks, respectively. Conclusion : The schedule of PEG-liposomal doxorubicin with 30–40 mg/m 2 every 4 weeks in combination with oral topotecan resulted in tumor response, but the toxicity was high. An individualized increasing dose of PEG-liposomal doxorubicin 10–20 mg/m 2 every two weeks is now recommended.