Abstract |
One of a novel series of compounds (AMAPS or arylmethylaminopropanediols), 773U82-HCl has shown significant antitumor activity in in vitro and in in vivo tumor systems, but has less animal CNS toxicity than the lead compound in the same series ( crisnatol). This study was designed to evaluate the pharmacokinetics, qualitative and quantitative toxicities of 773U82-HCl and to determine the recommended phase II dose (MTD) of 773U82-HCl given as a short infusion daily for 3 days every 3 weeks. Twenty-nine patients with refractory malignancies received 79 courses over 9 dose levels during this study. Doses ranged from 50 to 1060 mg/m2/d x 3 days. Due to the possibility of local hemolysis with concentrations > 1.5 mg/ml, drug was administered in solutions containing < or = 1.5 mg/ml. Because large volumes were needed at the higher dose levels, the infusion duration was increased from 2 hours to 4 hours. Mild to moderate nausea, vomiting, fatigue, dizziness and headaches were observed. Myelosuppression was the dose limiting toxicity. The recommended phase II dose and schedule was determined to be 800 mg/m2/d x 3d every 3 weeks. 773U82-HCl plasma concentration-time data were analyzed using a two-compartment pharmacokinetic model. The t1/2 beta averaged 6 hours and the total body clearance was 75.9 L/hr/m2. The volume of distribution (Vdss) was large, averaging 470 L/m2.
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Authors | H Bailey, P Kohler, R Tuttle, P P Carbone, J A Hohneker, N J Clendeninn, G Wilding |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 10
Issue 4
Pg. 279-87
(Nov 1992)
ISSN: 0167-6997 [Print] United States |
PMID | 1487401
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents
- Fluorenes
- Propylene Glycols
- 1,3-propanediol, 2-((3-fluoranthenylmethyl)amino)-2-methyl-
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Topics |
- Adult
- Aged
- Antineoplastic Agents
(administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
- Drug Administration Schedule
- Female
- Fluorenes
(administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
- Humans
- Infusions, Intravenous
- Male
- Middle Aged
- Neoplasms
(drug therapy)
- Propylene Glycols
(administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
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