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

AbstractBACKGROUND:
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.
AuthorsNobuko Hijiya, Clinton F Stewart, Yinmei Zhou, Dario Campana, Elaine Coustan-Smith, Gaston K Rivera, Mary V Relling, Ching-Hon Pui, Amar Gajjar
JournalCancer (Cancer) Vol. 112 Issue 9 Pg. 1983-91 (May 01 2008) ISSN: 0008-543X [Print] United States
PMID18318429 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Vincristine
  • Topotecan
  • Dexamethasone
  • Asparaginase
Topics
  • 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, mortality)
  • Recurrence
  • Topotecan (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
  • Vincristine (administration & dosage)

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