A phase II study of combined methotrexate and teniposide infusions prior to reinduction therapy in relapsed childhood acute lymphoblastic leukemia: A pediatric oncology group study

Judith Ochs, John Rodman, Minnie Abromowitch, Ronald Kavanagh, Michael Harris, Jack Yalowich, Gaston K. Rivera

Research output: Contribution to journalArticle

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Abstract

Teniposide (VM-26) con increase intracellular methotrexate (MTX) and its polyglutamate derivatives in vitro and thus has the potential to improve the therapeutic index of regimens containing MTX. In this phase II study, children and adolescents with acute lymphoblastic leukemia (ALL) in first or second marrow relapse were randomly assigned to receive either simultaneous (n = 11) or sequential (n = 12) continuous infusions of MTX and VM-26 prior to reinduction. Infusions of VM-26 were begun 12 hours after completion of MTX infusion in the sequential group. Dosages were individually adjusted to maintain plasma concentration levels of 10 μm for MTX and 15 μm for VM-26; total infusion times were 24 and 72 hours, respectively. Significant toxicity in the first six patients who received the scheduled 72-hour VM-26 infusion (including one drug-related death) prompted a 50% reduc-tion in infusion duration. The reduced dose was associated with similar but more manageable toxicity. Examination of bone marrow aspirates 10 days after therapy was begun showed one complete and two partial marrow remissions; a fourth patient who had an aplastic marrow on day 10 received no further chemotherapy and had a complete remission (CR) documented on day 31. There was no obvious clinical advantage associated with either infusion schedule, although small sample sizes preclude definitive conclusions. The 17% response rate to the MTX/VM-26 therapeutic window in patients with refractory disease suggests the need for further investigation to evaluate alternative schedules and concomitant therapy for this drug combination.

Original languageEnglish (US)
Pages (from-to)139-144
Number of pages6
JournalJournal of Clinical Oncology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 1991

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Teniposide
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Pediatrics
Bone Marrow
Therapeutics
Appointments and Schedules
Bone Marrow Examination
Combination Drug Therapy
Sample Size
Recurrence
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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A phase II study of combined methotrexate and teniposide infusions prior to reinduction therapy in relapsed childhood acute lymphoblastic leukemia : A pediatric oncology group study. / Ochs, Judith; Rodman, John; Abromowitch, Minnie; Kavanagh, Ronald; Harris, Michael; Yalowich, Jack; Rivera, Gaston K.

In: Journal of Clinical Oncology, Vol. 9, No. 1, 01.01.1991, p. 139-144.

Research output: Contribution to journalArticle

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abstract = "Teniposide (VM-26) con increase intracellular methotrexate (MTX) and its polyglutamate derivatives in vitro and thus has the potential to improve the therapeutic index of regimens containing MTX. In this phase II study, children and adolescents with acute lymphoblastic leukemia (ALL) in first or second marrow relapse were randomly assigned to receive either simultaneous (n = 11) or sequential (n = 12) continuous infusions of MTX and VM-26 prior to reinduction. Infusions of VM-26 were begun 12 hours after completion of MTX infusion in the sequential group. Dosages were individually adjusted to maintain plasma concentration levels of 10 μm for MTX and 15 μm for VM-26; total infusion times were 24 and 72 hours, respectively. Significant toxicity in the first six patients who received the scheduled 72-hour VM-26 infusion (including one drug-related death) prompted a 50{\%} reduc-tion in infusion duration. The reduced dose was associated with similar but more manageable toxicity. Examination of bone marrow aspirates 10 days after therapy was begun showed one complete and two partial marrow remissions; a fourth patient who had an aplastic marrow on day 10 received no further chemotherapy and had a complete remission (CR) documented on day 31. There was no obvious clinical advantage associated with either infusion schedule, although small sample sizes preclude definitive conclusions. The 17{\%} response rate to the MTX/VM-26 therapeutic window in patients with refractory disease suggests the need for further investigation to evaluate alternative schedules and concomitant therapy for this drug combination.",
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