Oral topotecan in children with recurrent or progressive high-grade glioma: a Phase I/II study by the German Society for Pediatric Oncology and Hematology

Cancer. 2004 Apr 15;100(8):1750-7. doi: 10.1002/cncr.20168.


Background: Continuous oral treatment with topotecan may be more effective than the typical 1-day and 5-day treatment schedules. In previous studies of continuous treatment with topotecan, increased intestinal side effects were reported in adult patients; however, the experience in pediatric patients and patients with high-grade glioma is quite limited.

Methods: Thirty-two pediatric patients with recurrent high-grade glioma (16 females and 16 males; median age, 9.5 years) were enrolled in the current Phase I/II study. Tumor locations included the cerebral cortex (n = 5), pons (n = 18), and other sites (n = 9). An injectable formulation of topotecan was administered orally, in ice-cold orange juice, once daily. The starting dose of 0.4 mg/m(2) per day was escalated on a patient-by-patient basis. At each patient's maximum dose, blood samples were obtained for the determination of plasma hydroxytopotecan and topotecan lactone concentrations and for the calculation of pharmacokinetic quantities.

Results: The toxicity criteria for a maximum tolerated topotecan dose were met in only 19 patients. The primary toxicity type was hematologic. The median maximum tolerated dose was 0.9 mg/m(2) per day (n = 19). The calculated maximum total plasma topotecan concentration was 3.8 ng/mL (n = 7), with an area under the concentration-time curve of 38.4 ng. hours/mL and a half-life of 4.1 hours, which would result in the complete disappearance of topotecan from the plasma after 12 hours. Objective responses were observed in 2 of 13 evaluable patients and lasted for 2.5 and 9 months, respectively (continuous clinical remission, 1 of 14 patients; partial response, 2 of 14 patients; stable disease, 7 of 14 patients; progressive disease, 4 of 14 patients).

Conclusions: Oral topotecan (median dose, 0.9 mg/m(2) per day) administered once daily was well tolerated and somewhat effective in children with recurrent high-grade glioma. A schedule in which the daily dose is split so that dosing is performed twice daily may be superior to the current schedule.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Female
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Male
  • Topotecan / administration & dosage
  • Topotecan / adverse effects
  • Topotecan / pharmacokinetics
  • Topotecan / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents
  • Topotecan