Hematological and Biochemical Action of Tiazofurin (NSC 286193) in a Case of Refractory Acute Myeloid Leukemia

Guido J. Tricot, Hiremagalur N. Jayaram, Craig R. Nichols, Kenneth Pennington, Elizabeth Lapis, George Weber, Ronald Hoffman

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Abstract

A patient with refractory acute myeloid leukemia was treated with tiazofurin, an agent that causes inhibition of tumor cell proliferation by depressing glutamic pyruvate transaminase concentrations in the malignant cells. The initial dose of 1100 mg/m2 was ineffective clinically and biochemically. Dose escalations to 1650, 2200, and finally 3300 mg/m2 resulted in a marked decrease in the absolute number of blasts without causing bone marrow hypoplasia or marked neutropenia. The decrease in the peripheral blast cell count was observed subsequent to a decline in glutamic pyruvate transaminase concentrations in the leukemic cells to < 30% of the pretreatment value. Consecutive bone marrow examinations showed a remarkable shift from myeloblasts to more mature myeloid elements, suggesting an in vivo differentiative action of tiazofurin. Although a total dose of 23,650 mg/m2 was administered over a 13-day period, only very mild side effects were noted. The absence of complications reported by others in Phase I trials with tiazofurin may be related to our slow administration of the drug by pump over a 1-h period in this trial. Tiazofurin appears to be a promising agent in the treatment of leukemia because of its selective action on leukemic cells and the availability of a rapid in vitro method capable of predicting sensitivity of leukemic cells to the agent and monitoring its activity during treatment by measuring thiazole-4-carboxamide adenine dinucleotide and glutamic pyruvate transaminase concentrations. These observations are being tested in a larger group of leukemic patients.

Original languageEnglish (US)
Pages (from-to)4988-4991
Number of pages4
JournalCancer Research
Volume47
Issue number18
StatePublished - Sep 15 1987

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tricot, G. J., Jayaram, H. N., Nichols, C. R., Pennington, K., Lapis, E., Weber, G., & Hoffman, R. (1987). Hematological and Biochemical Action of Tiazofurin (NSC 286193) in a Case of Refractory Acute Myeloid Leukemia. Cancer Research, 47(18), 4988-4991.