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Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion - Investigational New Drugs

  • ️Collins, Jerry M.
  • ️Sun Dec 01 1985

Summary

Tiazofurin (2-β-D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M2. Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 ± 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.

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Abbreviations

TCAR:

Tiazofurin

HPLC:

High performance liquid chromatography

IMPD:

Inosine monophosphate dehydrogenase

WBC:

white blood cell

CPK:

creatine phosphokinase

Css :

steady-state concentration

References

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Author information

Authors and Affiliations

  1. Clinical Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, Bethesda

    Gerald Batist, Raymond W. Klecker Jr., Jean F. Jenkins, John Grygiel, Robert L. Fine, Ian G. Kerr & Jerry M. Collins

  2. NCI-Navy Branches, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, Bethesda

    Daniel C. Ihde & Joyce L. Eddy

  3. Laboratory of Medicinal Chemistry and Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, Bethesda

    Hiremagalur N. Jayaram

Authors

  1. Gerald Batist

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  2. Raymond W. Klecker Jr.

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  3. Hiremagalur N. Jayaram

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  4. Jean F. Jenkins

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  5. John Grygiel

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  6. Daniel C. Ihde

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  7. Joyce L. Eddy

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  8. Robert L. Fine

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  9. Ian G. Kerr

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  10. Jerry M. Collins

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Batist, G., Klecker, R.W., Jayaram, H.N. et al. Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion. Invest New Drugs 3, 349–355 (1985). https://doi.org/10.1007/BF00170757

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  • Issue Date: December 1985

  • DOI: https://doi.org/10.1007/BF00170757

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