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.
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.
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.
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.
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA. nhijiya [at] childrensmemorial.org
Cancer. 2008 May;112(9):1983-91
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