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.


CONCLUSIONS
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.
Wagner
Sabine
S
Department of Pediatric Oncology, Krankenhaus der Barmherzigen Brüder, Klinik St. Hedwig, Steinmetzstrasse 1-3, Regensburg, Germany. sabine.wagner@barmherzige-regensburg.de
Peters
Ove
O
Fels
Christin
C
Janssen
Gisela
G
Liebeskind
Anne-Kathrin
AK
Sauerbrey
Axel
A
Suttorp
Meinolf
M
Hau
Peter
P
Wolff
Johannes E A
JE
D000284:Administration, Oral; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016545:Choroid Plexus Neoplasms / Q000188:drug therapy / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D003875:Drug Eruptions; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012008:Recurrence; D012189:Retrospective Studies; D013280:Stomatitis / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D019772:Topotecan; D004317:Doxorubicin