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).