Phase I study of etoposide phosphate (etopophos) as a 30-minute infusion on days 1, 3, and 5.

Etoposide phophate is a phosphate ester prodrug of etoposide designed to improve the pharmaceutical characteristics of the parent compound. A Phase I dose-escalating study of etoposide phosphate was conducted concurrently at two institutions to determine its toxicity, pharmacokinetics, and maximum tolerated dose. Etoposide phosphate was administered i.v. for 30 min on days 1, 3, and 5 every 21 days or on recovery from toxicity. Cohorts of at least three patients received etoposide phosphate at dose levels from 50 mg/m2 to 150 mg/m2 expressed as molar equivalents of etoposide. Blood and urine samples were obtained from all patients during the first cycle of treatment and the concentrations of etoposide phosphate and etoposide were measured. Thirty-nine patients with documented cancers received a total of 75 cycles of etoposide phosphate. The dose-limiting toxicity was myelosuppression which occurred at the 150-mg/m2 etoposide equivalent dose. Etoposide phosphate was rapidly and extensively converted to etoposide. No measurable etoposide phosphate was detectable in the plasma by 15-60 min after the end of the infusion. The mean half-life of etoposide at the different dose levels ranged from 5.5 to 9.3 h. The pharmacokinetics of etoposide, generated from etoposide phosphate, was linear over the dose range studied and was comparable to results reported in the literature for i.v. etoposide. In summary, i.v. etoposide phosphate is rapidly and extensively converted to etoposide. The maximum tolerated dose of etoposide phosphate when given on days 1, 3, and 5 is 150 mg/m2/day. The dose-limiting toxicity is myelosuppression. The maximum tolerated dose and adverse event profile are consistent with those of etoposide.

A chicken transferrin binding protein is heat shock protein 108.

A previously described transferrin binding protein from chicken oviduct has been identified as a heat shock protein, HSP108, by microsequencing of RP-HPLC purified tryptic peptides. The protein purified from oviduct by SDS-PAGE or from liver by ovotransferrin-affinity chromatography reacts with a monoclonal antibody raised against HSP108. The cDNA sequence predicts of KDEL peptide at the carboxyl terminus, but the protein does not react with anti-KDEL monoclonal antibodies, suggesting that HSP108 is processed in a way that eliminates the KDEL epitope.