Phase I and pharmacokinetic study of a water-soluble etoposide prodrug, etoposide phosphate (BMY-40481).
Etoposide phosphate is a water-soluble prodrug of etoposide. A phase I and pharmacokinetic study has been performed over the dose range 25-110 mg/m2/day for 5 days (etoposide equivalent doses). The maximum tolerated dose (MTD) was 110 mg/m2/day for 5 days every 3 weeks and the dose-limiting toxicity was neutropenia. Other toxicities were mild, with the exception of 2 patients who displayed significant hypersensitivity reactions. The etoposide phosphate:etoposide area under the plasma concentration versus time curve (AUC) ratio was < 1% and the pharmacokinetic parameters for etoposide were within previously reported ranges. Pharmacodynamic analyses demonstrated that etoposide AUC and baseline white blood cell count were significant determinants of leucopenia (model r2 = 0.51).
Millward
M J
MJ
University Department of Clinical Oncology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
Newell
D R
DR
Mummaneni
V
V
Igwemezie
L N
LN
Balmanno
K
K
Charlton
C J
CJ
Gumbrell
L
L
Lind
M J
MJ
Chapman
F
F
Proctor
M
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D011355:Prodrugs; C061400:etoposide phosphate; D005047:Etoposide