Phase I and pharmacokinetic study of 502U83 (an arylmethylaminopropanediol) in cancer patients.
502U83, a novel arylmethylaminopropanediol, has proven active in vivo against a panel of murine leukemia and solid tumors as well as in a tumor clonogenic assay against a variety of fresh human cancers. A total of 35 previously treated cancer patients were enrolled in a phase I study of this compound. The maximally tolerated dose (MTD) appears to be 12,800 mg/m2/72 h by continuous intravenous infusion with severe granulocytopenia occurring in three of five patients. There were no objective clinical responses. Serum pharmacokinetic parameters were as follows: plasma terminal phase half-life (t1/2 beta) = 3.84 h; total body clearance (CLB) = 53.1 l/h/m2; volume of distribution at steady state (Vdss) = 127.9 l/m2; maximum plasma concentration (Cmax) = 3.7 micrograms/ml (at 12,800 mg/m2/72 h dose).
Lam
K S
KS
Department of Medicine, University of Arizona, Tucson 85724.
Alberts
D S
DS
Peng
Y M
YM
Brodar
F
F
Matias
B
B
Modiano
M
M
Tuttle
R
R
Sol Lucas
V
V
Wargin
W
W
D000873:Anthracenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D004341:Drug Evaluation; D005260:Female; D006207:Half-Life; D006801:Humans; D007364:Intercalating Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000873:Anthracenes; D000970:Antineoplastic Agents; D007364:Intercalating Agents; C066521:502U83