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Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia

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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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Acknowledgments

Pediatric Oncology Group Chair Discretionary Fund; AMA-Educational and Research Foundation Florence Carter Fellowship Award; POG grant, 1979 to March 2003: CA 30969. A complete listing of grant support for research conducted by CCG and POG before initiation of the COG grant in 2003 is available online at: http://www.childrensoncologygroup.org/admin/grantinfo.htm.

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Authors and Affiliations

  1. Texas Children’s Cancer Center, Baylor College of Medicine, 6621 Fannin St MC, Houston, TX, 77030-2399, USA

    Patrick A. Thompson, Susan M. Blaney, Stacey L. Berg, ZoAnn E. Dreyer & Lisa R. Bomgaars

  2. Department of Pharmacology, University of Iowa, Iowa City, IA, USA

    Daryl J. Murry

  3. Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA

    Gary L. Rosner

  4. Institute of Statistics and Decision Sciences, Duke University, Durham, NC, 27708, USA

    Simon Lunagomez

  5. Midwest Children’s Cancer Center, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Bruce M. Camitta

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  1. Patrick A. Thompson
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  2. Daryl J. Murry
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  3. Gary L. Rosner
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  4. Simon Lunagomez
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  5. Susan M. Blaney
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  6. Stacey L. Berg
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  7. Bruce M. Camitta
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  8. ZoAnn E. Dreyer
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  9. Lisa R. Bomgaars
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Corresponding author

Correspondence to Lisa R. Bomgaars.

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Thompson, P.A., Murry, D.J., Rosner, G.L. et al. Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia. Cancer Chemother Pharmacol 59, 847–853 (2007). https://doi.org/10.1007/s00280-006-0388-1

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  • DOI: https://doi.org/10.1007/s00280-006-0388-1

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