Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia

Patrick A. Thompson, Daryl J. Murry, Gary Rosner, Simon Lunagomez, Susan M. Blaney, Stacey L. Berg, Bruce M. Camitta, ZoAnn E. Dreyer, Lisa R. Bomgaars

Research output: Contribution to journalArticle

Abstract

Purpose: We performed a pharmacokinetic evaluation of methotrexate (MTX) in infants with acute lymphoblastic leukemia enrolled on the Pediatric Oncology Group (POG) 9407 Infant Leukemia Study to evaluate the effects of age on MTX pharmacokinetics and pharmacodynamics. Methods: A pharmacokinetic database of 61 patients was developed by combining MTX data obtained from 16 patients in a pharmacokinetic sub-study with data obtained for clinical care in other patients enrolled on the POG 9407 protocol. The data were analyzed for the first dose of MTX given to patients in induction/intensification therapy. Patients received MTX (4 g/m2) over 24 h at week 4 of therapy. Toxicity data were also reviewed to evaluate the incidence of common MTX toxicities during the first 6 weeks of therapy (the induction/intensification phase). Results: Steady-state clearance (mean ± standard deviation) for infants aged 0-6 months was 89 ± 32 ml/min/m2 compared to 111 ± 40 for infants aged 7-12 months (P = 0.030). In the subgroup of infants aged 0-3 months the mean steady-state clearance was 84 ± 30 ml/min/m2 (P = 0.026 vs. the 7-12-month group). The incidence of renal toxicity (all grades) during induction/intensification therapy was 23% in the 0-3 months age group compared to 0% (for n = 27) in the group 7-12 months of age (P = 0.029). There were no significant differences in hepatoxicity or mucous membrane toxicity between age groups. Conclusions: A modest difference in steady-state MTX clearance is observed between younger infants (0-6 months) and older infants (7-12 months). Very young infants (0-3 months) also experienced a slightly higher incidence of renal toxicity during induction/intensification therapy. Steady-state clearance for the older infants is similar to values reported for children in other studies.

Original languageEnglish (US)
Pages (from-to)847-853
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume59
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

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Pharmacokinetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Toxicity
Pediatrics
Oncology
Pharmacodynamics
Incidence
Age Groups
Kidney
Therapeutics
Leukemia
Mucous Membrane
Databases

Keywords

  • Infants
  • Leukemia
  • Methotrexate
  • Pediatrics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Thompson, P. A., Murry, D. J., Rosner, G., Lunagomez, S., Blaney, S. M., Berg, S. L., ... Bomgaars, L. R. (2007). Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia. Cancer Chemotherapy and Pharmacology, 59(6), 847-853. https://doi.org/10.1007/s00280-006-0388-1

Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia. / Thompson, Patrick A.; Murry, Daryl J.; Rosner, Gary; Lunagomez, Simon; Blaney, Susan M.; Berg, Stacey L.; Camitta, Bruce M.; Dreyer, ZoAnn E.; Bomgaars, Lisa R.

In: Cancer Chemotherapy and Pharmacology, Vol. 59, No. 6, 06.2007, p. 847-853.

Research output: Contribution to journalArticle

Thompson, PA, Murry, DJ, Rosner, G, Lunagomez, S, Blaney, SM, Berg, SL, Camitta, BM, Dreyer, ZE & Bomgaars, LR 2007, 'Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia', Cancer Chemotherapy and Pharmacology, vol. 59, no. 6, pp. 847-853. https://doi.org/10.1007/s00280-006-0388-1
Thompson, Patrick A. ; Murry, Daryl J. ; Rosner, Gary ; Lunagomez, Simon ; Blaney, Susan M. ; Berg, Stacey L. ; Camitta, Bruce M. ; Dreyer, ZoAnn E. ; Bomgaars, Lisa R. / Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia. In: Cancer Chemotherapy and Pharmacology. 2007 ; Vol. 59, No. 6. pp. 847-853.
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abstract = "Purpose: We performed a pharmacokinetic evaluation of methotrexate (MTX) in infants with acute lymphoblastic leukemia enrolled on the Pediatric Oncology Group (POG) 9407 Infant Leukemia Study to evaluate the effects of age on MTX pharmacokinetics and pharmacodynamics. Methods: A pharmacokinetic database of 61 patients was developed by combining MTX data obtained from 16 patients in a pharmacokinetic sub-study with data obtained for clinical care in other patients enrolled on the POG 9407 protocol. The data were analyzed for the first dose of MTX given to patients in induction/intensification therapy. Patients received MTX (4 g/m2) over 24 h at week 4 of therapy. Toxicity data were also reviewed to evaluate the incidence of common MTX toxicities during the first 6 weeks of therapy (the induction/intensification phase). Results: Steady-state clearance (mean ± standard deviation) for infants aged 0-6 months was 89 ± 32 ml/min/m2 compared to 111 ± 40 for infants aged 7-12 months (P = 0.030). In the subgroup of infants aged 0-3 months the mean steady-state clearance was 84 ± 30 ml/min/m2 (P = 0.026 vs. the 7-12-month group). The incidence of renal toxicity (all grades) during induction/intensification therapy was 23{\%} in the 0-3 months age group compared to 0{\%} (for n = 27) in the group 7-12 months of age (P = 0.029). There were no significant differences in hepatoxicity or mucous membrane toxicity between age groups. Conclusions: A modest difference in steady-state MTX clearance is observed between younger infants (0-6 months) and older infants (7-12 months). Very young infants (0-3 months) also experienced a slightly higher incidence of renal toxicity during induction/intensification therapy. Steady-state clearance for the older infants is similar to values reported for children in other studies.",
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T1 - Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia

AU - Thompson, Patrick A.

AU - Murry, Daryl J.

AU - Rosner, Gary

AU - Lunagomez, Simon

AU - Blaney, Susan M.

AU - Berg, Stacey L.

AU - Camitta, Bruce M.

AU - Dreyer, ZoAnn E.

AU - Bomgaars, Lisa R.

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N2 - Purpose: We performed a pharmacokinetic evaluation of methotrexate (MTX) in infants with acute lymphoblastic leukemia enrolled on the Pediatric Oncology Group (POG) 9407 Infant Leukemia Study to evaluate the effects of age on MTX pharmacokinetics and pharmacodynamics. Methods: A pharmacokinetic database of 61 patients was developed by combining MTX data obtained from 16 patients in a pharmacokinetic sub-study with data obtained for clinical care in other patients enrolled on the POG 9407 protocol. The data were analyzed for the first dose of MTX given to patients in induction/intensification therapy. Patients received MTX (4 g/m2) over 24 h at week 4 of therapy. Toxicity data were also reviewed to evaluate the incidence of common MTX toxicities during the first 6 weeks of therapy (the induction/intensification phase). Results: Steady-state clearance (mean ± standard deviation) for infants aged 0-6 months was 89 ± 32 ml/min/m2 compared to 111 ± 40 for infants aged 7-12 months (P = 0.030). In the subgroup of infants aged 0-3 months the mean steady-state clearance was 84 ± 30 ml/min/m2 (P = 0.026 vs. the 7-12-month group). The incidence of renal toxicity (all grades) during induction/intensification therapy was 23% in the 0-3 months age group compared to 0% (for n = 27) in the group 7-12 months of age (P = 0.029). There were no significant differences in hepatoxicity or mucous membrane toxicity between age groups. Conclusions: A modest difference in steady-state MTX clearance is observed between younger infants (0-6 months) and older infants (7-12 months). Very young infants (0-3 months) also experienced a slightly higher incidence of renal toxicity during induction/intensification therapy. Steady-state clearance for the older infants is similar to values reported for children in other studies.

AB - Purpose: We performed a pharmacokinetic evaluation of methotrexate (MTX) in infants with acute lymphoblastic leukemia enrolled on the Pediatric Oncology Group (POG) 9407 Infant Leukemia Study to evaluate the effects of age on MTX pharmacokinetics and pharmacodynamics. Methods: A pharmacokinetic database of 61 patients was developed by combining MTX data obtained from 16 patients in a pharmacokinetic sub-study with data obtained for clinical care in other patients enrolled on the POG 9407 protocol. The data were analyzed for the first dose of MTX given to patients in induction/intensification therapy. Patients received MTX (4 g/m2) over 24 h at week 4 of therapy. Toxicity data were also reviewed to evaluate the incidence of common MTX toxicities during the first 6 weeks of therapy (the induction/intensification phase). Results: Steady-state clearance (mean ± standard deviation) for infants aged 0-6 months was 89 ± 32 ml/min/m2 compared to 111 ± 40 for infants aged 7-12 months (P = 0.030). In the subgroup of infants aged 0-3 months the mean steady-state clearance was 84 ± 30 ml/min/m2 (P = 0.026 vs. the 7-12-month group). The incidence of renal toxicity (all grades) during induction/intensification therapy was 23% in the 0-3 months age group compared to 0% (for n = 27) in the group 7-12 months of age (P = 0.029). There were no significant differences in hepatoxicity or mucous membrane toxicity between age groups. Conclusions: A modest difference in steady-state MTX clearance is observed between younger infants (0-6 months) and older infants (7-12 months). Very young infants (0-3 months) also experienced a slightly higher incidence of renal toxicity during induction/intensification therapy. Steady-state clearance for the older infants is similar to values reported for children in other studies.

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