Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse

Cancer. 2008 May 1;112(9):1983-91. doi: 10.1002/cncr.23395.


Background: The authors evaluated the response rate, toxicity, and pharmacokinetics of topotecan given before standard induction therapy for childhood acute lymphoblastic leukemia (ALL) in first relapse.

Methods: Patients received topotecan (2.4 mg/m(2) daily as a 30-minute infusion) for 5 days before induction therapy with dexamethasone, vincristine, and asparaginase (native or pegylated Escherichia coli). The pharmacokinetics of topotecan were measured with the first dose of treatment in 23 patients.

Results: Twenty-eight of 31 patients with circulating blast cells were evaluable for response to topotecan. Twenty-five patients (89.3%) had a response (>25% decrease in circulating blast cells). The leukocyte count (P = .0001) and blast cell count (P = .0009) declined significantly during topotecan therapy. The median (range) topotecan lactone area under the concentration-time curve after the first dose was 85.4 L/hour/m(2) (range, 38.7-229.3 L/hour/m(2)). At the end of induction, 23 patients (74.2%) had a complete response, 1 patient (3.2%) had a partial response, 5 patients (16.1%) had no response, and 2 patients had died of infection. Six of the 17 patients who were studied for minimal residual disease (MRD) achieved MRD-negative status at the end of induction. The main toxicities were hematologic, gastrointestinal, and hepatic. The estimated 5-year survival rate, event-free survival rate, and cumulative incidence of second relapse were 24.1% +/- 7.9%, 18.2% +/- 7.4%, and 22.8% +/- 8.7%, respectively, in the 29 patients who had a hematologic first relapse.

Conclusions: A regimen comprising single-agent topotecan given with a standard 3-drug combination was effective in inducing remission in pediatric patients with relapsed ALL and was tolerated well.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Child
  • Child, Preschool
  • Dexamethasone / administration & dosage
  • Female
  • Humans
  • Infant
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Recurrence
  • Topotecan / administration & dosage
  • Topotecan / adverse effects
  • Topotecan / pharmacokinetics
  • Topotecan / therapeutic use
  • Vincristine / administration & dosage


  • Vincristine
  • Topotecan
  • Dexamethasone
  • Asparaginase