TY - JOUR
T1 - High-dose mercaptopurine followed by intermediate-dose cytarabine in relapsed acute leukemia
AU - Lockhart, S.
AU - Plunkett, W.
AU - Jeha, S.
AU - Ramirez, I.
AU - Zipf, T.
AU - Cork, A.
AU - Pinkel, D.
PY - 1994/3
Y1 - 1994/3
N2 - Purpose: This phase I/II study was designed to explore the feasibility, toxicity, and potential efficacy of administering high-dose continuous intravenous mercaptopurine (6MP) followed by intermediate-dose continuous intravenous cytarabine (Ara-C) to children with relapsed or unresponsive acute leukemia. Patients and Methods: Twenty-three children with relapsed or unresponsive acute leukemia (13 myeloid, 10 lymphoid) were entered onto the study. After initial hydration and alkalinization, 1,000 or 1,250 mg/m2 of 6MP was administered by continuous intravenous infusion over 24 hours. Following another period of hydration, 500 mg/m2 of Ara-C was administered by continuous intravenous infusion daily for 4 days. In 17 children, plasma concentrations of 6MP were measured at hours 4, 24, and 27 of the 6MP infusions. Plasma concentrations of Ara-C were measured at hours 8, 24, 48, 72, and 96 of the Ara-C infusions. Intracellular Ara-C triphosphate (Ara- CTP) concentrations were measured in peripheral-blood leukemia cells of the five patients with sufficient cells for measurement. Children who developed remission received repeated courses of this regimen every 3 to 4 weeks until relapse or completion of 12 courses. Results: Of 13 children with acute myeloid leukemia (AMI), six developed complete remissions (CRs) lasting 7 months to nearly 4 years. Two children remain in CR with normal growth, development, and health 3 years after cessation of treatment. Of 10 children with acute lymphoid leukemia (ALL), one had a CR of 2 months' duration. Dose- limiting toxicity consisted of severe hematosuppression with fever, neutropenia, and serious infection. There were two toxic deaths. The mean steady-state plasma concentrations of 6MP were approximately 4 μmol/L and of Ara-C approximately 3 μmol/L. The median Ara-CTP concentration in peripheral-blood leukemia cells was 308 μmol/L at hour 8 of the Ara-C infusion. Conclusion: High-dose continuous intravenous 6MP followed by intermediate-dose intravenous Ara-C produced CRs of longer than 6 months in approximately half of children with relapsed or unresponsive AML. Further study of this drug regimen is justified.
AB - Purpose: This phase I/II study was designed to explore the feasibility, toxicity, and potential efficacy of administering high-dose continuous intravenous mercaptopurine (6MP) followed by intermediate-dose continuous intravenous cytarabine (Ara-C) to children with relapsed or unresponsive acute leukemia. Patients and Methods: Twenty-three children with relapsed or unresponsive acute leukemia (13 myeloid, 10 lymphoid) were entered onto the study. After initial hydration and alkalinization, 1,000 or 1,250 mg/m2 of 6MP was administered by continuous intravenous infusion over 24 hours. Following another period of hydration, 500 mg/m2 of Ara-C was administered by continuous intravenous infusion daily for 4 days. In 17 children, plasma concentrations of 6MP were measured at hours 4, 24, and 27 of the 6MP infusions. Plasma concentrations of Ara-C were measured at hours 8, 24, 48, 72, and 96 of the Ara-C infusions. Intracellular Ara-C triphosphate (Ara- CTP) concentrations were measured in peripheral-blood leukemia cells of the five patients with sufficient cells for measurement. Children who developed remission received repeated courses of this regimen every 3 to 4 weeks until relapse or completion of 12 courses. Results: Of 13 children with acute myeloid leukemia (AMI), six developed complete remissions (CRs) lasting 7 months to nearly 4 years. Two children remain in CR with normal growth, development, and health 3 years after cessation of treatment. Of 10 children with acute lymphoid leukemia (ALL), one had a CR of 2 months' duration. Dose- limiting toxicity consisted of severe hematosuppression with fever, neutropenia, and serious infection. There were two toxic deaths. The mean steady-state plasma concentrations of 6MP were approximately 4 μmol/L and of Ara-C approximately 3 μmol/L. The median Ara-CTP concentration in peripheral-blood leukemia cells was 308 μmol/L at hour 8 of the Ara-C infusion. Conclusion: High-dose continuous intravenous 6MP followed by intermediate-dose intravenous Ara-C produced CRs of longer than 6 months in approximately half of children with relapsed or unresponsive AML. Further study of this drug regimen is justified.
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U2 - 10.1200/JCO.1994.12.3.587
DO - 10.1200/JCO.1994.12.3.587
M3 - Article
C2 - 8120558
AN - SCOPUS:0028274980
SN - 0732-183X
VL - 12
SP - 587
EP - 595
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -