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 Citations (Scopus)

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 2008

Fingerprint

Aminopterin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Toxicity
Therapeutics
Folic Acid Antagonists
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Methylenetetrahydrofolate Reductase (NADPH2)
Poisons
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Polymorphism
Metabolism
Design of experiments
Biological Availability
Neutrophils
Research Design
Recurrence
Liver

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Cole, P. D., Drachtman, R. A., Masterson, M., Smith, A. K., Glod, J., Zebala, J. 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

Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia. / Cole, Peter D.; Drachtman, Richard A.; Masterson, Margaret; Smith, Angela K.; Glod, John; Zebala, John A.; Lisi, Stacey; Drapala, Drew Anne; Kamen, Barton A.

In: Cancer Chemotherapy and Pharmacology, Vol. 62, No. 1, 06.2008, p. 65-75.

Research output: Contribution to journalArticle

Cole, PD, Drachtman, RA, Masterson, M, Smith, AK, Glod, J, Zebala, JA, Lisi, S, Drapala, DA & Kamen, BA 2008, 'Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia', Cancer Chemotherapy and Pharmacology, vol. 62, no. 1, pp. 65-75. https://doi.org/10.1007/s00280-007-0576-7
Cole, Peter D. ; Drachtman, Richard A. ; Masterson, Margaret ; Smith, Angela K. ; Glod, John ; Zebala, John A. ; Lisi, Stacey ; Drapala, Drew Anne ; Kamen, Barton A. / Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia. In: Cancer Chemotherapy and Pharmacology. 2008 ; Vol. 62, No. 1. pp. 65-75.
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