title: Intraventricular etoposide safety and toxicity profile in children and young adults with refractory or recurrent malignant brain tumors.
abstract: Systemic administration of etoposide is effective in treating metastatic, recurrent or refractory brain tumors, but penetration into the cerebrospinal fluid is extremely poor. This study was designed to determine the safety and toxicity profile of intraventricular etoposide administration and was affiliated with the prospective, multicenter, nonblinded, nonrandomized, multi-armed HIT-REZ-97 trial. The study enrolled 68 patients, aged 1.1-34.6 (median age 11 years). Adverse events that could possibly be related to intraventricular etoposide therapy were documented and analyzed. Intraventricular etoposide was simultaneously administered with either oral or intravenous chemotherapy in 426 courses according to three major schedules varying in dosing (0.25-1 mg), frequency of administration (bolus injection, every 12 or 24 h), course duration (5-10 days) and length of interval between courses (2-5 weeks). Potential treatment-related adverse effects included transient headache, seizures, infection of the reservoir, nausea and neuropsychological symptoms. Hematological side effects were not observed. One patient, with history of multiple prior therapies, who received long-term intraventricular and oral etoposide treatment developed acute myeloid leukemia as a secondary malignancy. Overall intraventricular etoposide is well tolerated. The results of this study have warranted a phase II trial to determine the effectiveness of this regimen in disease stages with very limited therapeutic options.
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany. k.pajtler@dkfz-heidelberg.de.|Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. k.pajtler@dkfz-heidelberg.de.
authors.forename: Kristian W
authors.initials: KW
authors.lastname: Pajtler
authors.affiliation: Department of Pediatric Oncology and Hematology, Pediatrics III, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Tippelt
authors.affiliation: Department of Pediatric Oncology and Hematology, Pediatrics III, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Nele
authors.initials: N
authors.lastname: Siegler
authors.affiliation: Department of Pediatric Hematology and Oncology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Reichling
authors.affiliation: Department of Pediatric Hematology and Oncology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Department of Pediatric Oncology and Hematology, Pediatrics III, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Mikasch
authors.affiliation: Department of Pediatric Hematology and Oncology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Bode
authors.affiliation: Hospital for Children and Adolescents, Klinikum Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Gnekow
authors.affiliation: Institute of Neuropathology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.affiliation: Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.affiliation: Department of Pediatric Oncology and Hematology, Pediatrics III, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Fleischhack
mesh_terms: D000293:Adolescent; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D002552:Cerebral Ventricles; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide
keywords: ATRT; Ependymoma; Medulloblastoma; Pediatric brain tumors; Progression; Relapse