Phase 2 clinical trial of intrathecal topotecan in children with refractory leptomeningeal leukemia: a Children's Oncology Group trial (P9962)

Pediatr Blood Cancer. 2012 Mar;58(3):362-5. doi: 10.1002/pbc.23317. Epub 2011 Sep 9.


Purpose: We performed a phase 2 study in children with recurrent or refractory leptomeningeal leukemia to determine the objective response rate after treatment with intrathecal (IT) topotecan.

Patients and methods: Patients received age-adjusted IT topotecan (0.4 mg/dose for patients >3 years of age) administered twice weekly (every 3-4 days) for 6 weeks during induction, weekly for 4 weeks during consolidation, and twice monthly for 4 months and then monthly thereafter during maintenance.

Results: Twenty-two patients enrolled in the study, of whom 20 were eligible and assessable for toxicity and 16 were assessable for response. Of 16 patients, 6 (38%) had a complete response, 8 (50%) had stable disease, and 2 (13%) had progressive disease. The median event-free survival time (95% CI) was 3.1 (1.6-10.3) months and the median overall survival time (95% CI) was 18.0 (7.3-38.3) months. Eight patients (40%) experienced grade 3 or 4 adverse events. There were no grade 4 neurological events (Table III). Four patients experienced a total of 6 grade 3 neurological events including an olfactory seizure, a headache, transient grade 3 speech impairment, muscle weakness, motor neuropathy, and ataxia. Headache was the most common grade ≤2 neurologic event and two patients developed grade ≤2 arachnoiditis.

Conclusion: IT administration of topotecan was tolerable on this dose and schedule. The majority of adverse events were mild to moderate, reversible side effects. Complete central nervous system remissions were achieved in a subset of children with recurrent or refractory central nervous system leukemia.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Spinal
  • Leukemia / drug therapy*
  • Male
  • Meningeal Neoplasms / drug therapy*
  • Neoplasm Recurrence, Local / drug therapy
  • Survival Analysis
  • Topoisomerase I Inhibitors / administration & dosage*
  • Topoisomerase I Inhibitors / adverse effects
  • Topotecan / administration & dosage*
  • Topotecan / adverse effects
  • Young Adult


  • Topoisomerase I Inhibitors
  • Topotecan