title: Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: a multi-institutional retrospective study.
abstract: This retrospective study aimed to evaluate the safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with refractory or recurrent brain tumors. Nineteen heavily pretreated patients (males, n = 14; females, n = 5; median age at diagnosis 8.5 years; range, 1.4-22 years) were given intrathecal liposomal cytarabine on a compassionate use basis for recurrent refractory medulloblastoma (n = 12), mixed germ cell tumor (n = 2), central nervous system primitive neuroectodermal tumors of the pons (n = 1), anaplastic ependymoma (n = 1), anaplastic oligodendroglioma (n = 1), atypical teratoid rhabdoid tumor (n = 1), or rhabdoid papillary meningioma (n = 1). Eighteen patients received concomitant systemic radiochemotherapy. A total of 88 intrathecal injections of liposomal cytarabine (dose range, 20-50 mg) were administered with concomitant dexamethasone prophylaxis. The median number of doses per patient was four (range, 1-10). Duration of treatment ranged from (1/2) to 10 months. Eleven patients (57.9%) did not show any side effects, whereas eight patients (42.1%) developed side effects related to either chemical arachnoiditis (n = 4) or neurological progression (n = 2). Less typical treatment-related symptoms (e.g. lethargy, ataxia, and slurred speech) were observed in two patients. Treatment with intrathecal liposomal cytarabine was discontinued twice because of side effects. In conclusion, although intrathecal liposomal cytarabine was generally well tolerated, it should be used cautiously and only with dexamethasone prophylaxis in extensively pretreated patients with recurrent brain tumors. Proof of efficacy requires a prospective single-agent phase II study.
authors.affiliation: Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria. martin.benesch@klinikum-graz.at
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.forename: Nele
authors.initials: N
authors.lastname: Siegler
authors.forename: Katja von
authors.initials: Kv
authors.lastname: Hoff
authors.forename: Lisa
authors.initials: L
authors.lastname: Lassay
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kropshofer
authors.forename: Hermann
authors.initials: H
authors.lastname: Müller
authors.forename: Constanze
authors.initials: C
authors.lastname: Sommer
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Gudrun
authors.initials: G
authors.lastname: Fleischhack
authors.forename: Christian
authors.initials: C
authors.lastname: Urban
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D057176:Compassionate Use Trials; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects*; D003692:Delayed-Action Preparations; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D012189:Retrospective Studies; D016879:Salvage Therapy; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D008081:Liposomes; D003561:Cytarabine