Clinical and Translational Oncology

, Volume 14, Issue 4, pp 280–286 | Cite as

Efficacy and safety of liposomal cytarabine in children with primary CNS tumours with leptomeningeal involvement

  • Aurora NavajasEmail author
  • Álvaro Lassaletta
  • Andrés Morales
  • Blanca López-Ibor
  • Constantino Sábado
  • Cristina Moscardó
  • Elena Mateos
  • Javier Molina
  • María Sagaseta
  • Ana Sastre
Research Articles



To assess the efficacy and safety of liposomal cytarabine in the treatment of de novo and relapsed leptomeningeal involvement in children with primary CNS tumours.


Data from clinical charts were entered into a database for consecutive unselected patients (n=20) from nine Spanish centres. Diagnosis of leptomeningeal involvement was confirmed by cytology, MRI and/or CT scan. The dose of liposomal cytarabine used varied from 20 to 50 mg, by age.


There were 8 females and 12 males, mean age 7.3 years (range 8 months to 18 years). The tumours were: 10 medulloblastomas, 4 ependymomas, 3 primitive neuroectodermal tumours and 3 other tumours. Fourteen had undergone previous chemotherapy and 12 radiotherapy. Nine received concurrent chemotherapy and 2 concurrent radiotherapy. Median follow-up was 244.5 days (range 12–869). Patients received a median of 5 doses (range 1–9) of liposomal cytarabine. A neurological response (complete or partial) was seen in 11/19 (58%) and a cytological response in 7/10 (64%). Median time to neurological progression exceeded 180 days (range 12–869). Adverse effects were reported in 11/20 patients, but none was grade IV.


Liposomal cytarabine was well tolerated and efficacious in this patient group, but prospective randomised trials are needed.


Leptomeningeal disease Brain tumour Intrathecal drug Paediatric 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Baldwin RT, Preston-Martin S (2004) Epidemiology of brain tumors in childhood: a review. Toxicol Appl Pharmacol 199:118–131PubMedCrossRefGoogle Scholar
  2. 2.
    Partap S, Fisher PG (2007) Update on new treatments and developments in childhood brain tumors. Curr Opin Pediatr 19:670–674PubMedCrossRefGoogle Scholar
  3. 3.
    Chamberlain MC (1995) A review of leptomeningeal metastases in pediatrics. J Child Neurol 10:191–199PubMedCrossRefGoogle Scholar
  4. 4.
    Kim S, Khatibi S, Howell SB et al (1993) Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam. Cancer Res 53:1596–1598PubMedGoogle Scholar
  5. 5.
    Chamberlain MC, Kormanik P, Howell SB et al (1995) Pharmacokinetics of intralumbar DTC-101 for the treatment of leptomeningeal metastases. Arch Neurol 52:912–917PubMedCrossRefGoogle Scholar
  6. 6.
    Glantz MJ, LaFollette S, Jaeckle KA et al (1999) Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 17:3110–3116PubMedGoogle Scholar
  7. 7.
    Phuphanich S, Maria B, Braeckman R et al (2007) A pharmacokinetic study of intra-CSF adminis tered encapsulated cytarabine (DepoCyt) for the treatment of neoplastic meningitis in patients with leukemia, lymphoma, or solid tumors as part of a phase III study. J Neurooncol 81:201–208PubMedCrossRefGoogle Scholar
  8. 8.
    Angst MS, Drover DR (2006) Pharmacology of drugs formulated with DepoFoam: a sustained release drug delivery system for parenteral administration using multivesicular liposome technology. Clin Pharmacokinet 45:1153–1176PubMedCrossRefGoogle Scholar
  9. 9.
    FDA. Depocyt Approval Letter. Available at: Accessed19 May 2011
  10. 10.
    EMEA. Depocyte European Public Assessment Report. Available at: pdf. Accessed 19 May 2011
  11. 11.
    Bomgaars L, Geyer JR, Franklin J et al (2004) Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis. J Clin Oncol 22:3916–3921PubMedCrossRefGoogle Scholar
  12. 12.
    Slavc I, Peyrl A, Gupper A et al (2006) Tolerability of intrathecal liposomal cytarabine at a dose 25–50 mg in children 11 months to 15 years old. 7th Congress EANO in Vienna, Austria, September 14–17, 2006. Abstract 130. Available at: Accessed 8 February 2008
  13. 13.
    Benesch M, Sovinz P, Krammer B et al (2007) Feasibility and toxicity of intrathecal liposomal cytarabine in 5 children and young adults with refractory neoplastic meningitis. J Pediatr Hematol Oncol 29:222–226PubMedCrossRefGoogle Scholar
  14. 14.
    Björgvinsdóttir H, Heldrup J, Békássy A et al (2006) Intrathecal liposomal cytarabine: clinical experience in pediatric leukemia and neuroblastoma patients. Pediatr Blood Cancer 47[Suppl 4]:444Google Scholar
  15. 15.
    Peyrl A, Sauermann R, Slavc I et al (2008) Safety and pharmacokinetics of intrathecal liposomal cytarabine (DepoCyte®) in children <= 3 years of age with malignant brain tumors. Presented at: 13th ISPNO International Symposium on Pediatric Neuro-Oncology, Chicago, USAGoogle Scholar
  16. 16.
    Lassaletta A, Navajas A, Sabado C et al (2007) Intrathecal liposomal cytarabine in children with brain tumors. Presented at: 39th Annual Conference SIOP, Mumbai, IndiaGoogle Scholar
  17. 17.
    Lassaletta A, Navajas A et al (2008) Intrathecal liposomal cytarabine in children with brain tumors. Presented at: SIOP 2008, 40th Annual Conference of International Society of Paediactric Oncology, Berlin, GermanyGoogle Scholar
  18. 18.
    Lassaletta A, Perez-Olleros P, Scaglione C et al (2007) Successful treatment of intracranial ependymoma with leptomeningeal spread with systemic chemotherapy and intrathecal liposomal cytarabine in a two-year-old child. J Neurooncol 83:303–306PubMedCrossRefGoogle Scholar
  19. 19.
    Napp Pharmaceuticals Limited (2009) Depo-Cyte 50 mg suspension for injection SPC. Available at: Accessed 27 February 2009
  20. 20.
    Sommer C, Lackner H, Benesch M et al (2008) Neuroophthalmological side effects following intrathecal administration of liposomal cytarabine for central nervous system prophylaxis in three adolescents with acute myeloid leukaemia. Ann Hematol 87:887–890PubMedCrossRefGoogle Scholar
  21. 21.
    Hospira. Cytarabine Injection Prescribing Information. Available at:

Copyright information

© Feseo 2012

Authors and Affiliations

  • Aurora Navajas
    • 1
    Email author
  • Álvaro Lassaletta
    • 2
  • Andrés Morales
    • 3
  • Blanca López-Ibor
    • 4
  • Constantino Sábado
    • 5
  • Cristina Moscardó
    • 6
  • Elena Mateos
    • 7
  • Javier Molina
    • 8
  • María Sagaseta
    • 8
  • Ana Sastre
    • 9
  1. 1.Hospital de CrucesBarakaldo, GuipúzcoaSpain
  2. 2.Hospital del Niño JesúsMadridSpain
  3. 3.Hospital Sant Joan de DeuBarcelonaSpain
  4. 4.Hospital MontepríncipeMadridSpain
  5. 5.Hospital Vall d’HebrónBarcelonaSpain
  6. 6.Hospital General de AlicanteAlicanteSpain
  7. 7.Hospital Reina SofíaCórdobaSpain
  8. 8.Hospital Virgen del Camino PamplonaNavarraSpain
  9. 9.Hospital Universitario La PazMadridSpain

Personalised recommendations