Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 349-355 |
| Number of pages | 7 |
| Journal | Investigational New Drugs |
| Volume | 3 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 1985 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
- Molecular Medicine
Cite this
Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion. / Batist, Gerald; Klecker, Raymond W.; Jayaram, Hiremagalur N.; Jenkins, Jean F.; Grygiel, John; Ihde, Daniel C.; Eddy, Joyce L.; Fine, Robert L.; Kerr, Ian G.; Collins, Jerry M.
In: Investigational New Drugs, Vol. 3, No. 4, 12.1985, p. 349-355.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion
AU - Batist, Gerald
AU - Klecker, Raymond W.
AU - Jayaram, Hiremagalur N.
AU - Jenkins, Jean F.
AU - Grygiel, John
AU - Ihde, Daniel C.
AU - Eddy, Joyce L.
AU - Fine, Robert L.
AU - Kerr, Ian G.
AU - Collins, Jerry M.
PY - 1985/12
Y1 - 1985/12
N2 - 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.
AB - 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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U2 - 10.1007/BF00170757
DO - 10.1007/BF00170757
M3 - Article
VL - 3
SP - 349
EP - 355
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 4
ER -