Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia

Peter D. Cole, Richard A. Drachtman, Margaret Masterson, Angela K. Smith, John Glod, John A. Zebala, Stacey Lisi, Drew Anne Drapala, Barton A. Kamen

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Purpose: Aminopterin offers advantages over the related antifolate, methotrexate, including greater potency, complete bioavailability, and more consistent accumulation and metabolism by patients' blasts. This current trial was done to document the toxicity of the aminopterin within a multiagent therapeutic regimen for children with newly diagnosed ALL. Experimental Design: Patients at high risk of relapse were non-randomly assigned to therapy including oral aminopterin 4 mg/m2, in two doses 12 h apart, in place of methotrexate 100 mg/m2 in four divided doses. Results: Thirty-two patients, 22 with pre-B ALL and ten with T-lineage ALL, have been treated with aminopterin, with median follow up of 40 months. Hematologic, mucosal and hepatic toxicity has been tolerable and reversible. There have been no toxic deaths among patients in remission. During weekly AMT therapy, higher mean neutrophil counts were observed among patients who were wild type for polymorphisms in methylene tetrahydrofolate reductase and methionine synthase reductase. Conclusions: Aminopterin can be safely incorporated in multiagent therapy for patients with ALL, in place of systemic methotrexate, without causing excessive toxicity. These results support a larger trial comparing the efficacy and toxicity of aminopterin and methotrexate in therapy for patients with ALL.

Original languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalCancer Chemotherapy and Pharmacology
Volume62
Issue number1
DOIs
StatePublished - Jun 1 2008

Keywords

  • Acute lymphoblastic leukemia
  • Aminopterin
  • Antifolate
  • Methotrexate
  • Therapeutic trial

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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    Cole, P. D., Drachtman, R. A., Masterson, M., Smith, A. K., Glod, J., Zebala, J. A., Lisi, S., Drapala, D. A., & Kamen, B. A. (2008). Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia. Cancer Chemotherapy and Pharmacology, 62(1), 65-75. https://doi.org/10.1007/s00280-007-0576-7