PNU-214565, a SAg-based tumor targeted therapy, is safe when given as a single 3-hour infusion at doses up to 1.5 ng/kg. The MTD for a single dose was not determined. The safety of a repeated dose schedule is currently under investigation, beginning with doses determined to be safe in this trial.

No abstract

ABSTRACT:In the present study, the involvement of cytochrome P450 enzyme (

Estramustine at concentrations ranging from 3-40 x 10(-6) M inhibited the cell growth and clonogenic survival of a human prostatic carcinoma cell line (DU 145). This cell line was found to be unresponsive to estradiol and testosterone at concentrations ranging from 10(-9) M to 5 x 10(-5) M. Metabolism studies with estramustine showed that only a few per cent of the ester linkage was cleaved during the exposure period. This small amount of metabolism could possibly lead to the release of nor-nitrogen mustard, which was however found not to be as inhibitory as estramustine in this cell line. The results indicate that estramustine per se causes the cell death of hormone unresponsive human prostatic carcinoma cells in cell culture.

Oestrogen-containing vaginal rings of various designs have been utilised in hormone replacement therapy. In contrast to the traditional ‘homogeneous’ design, rings designed with a steroid-containing core and outer polymer sheath provide a diffusion-controlled release rate which enables the delivery of low doses of drug. The aim of this investigation was to evaluate in vitro oestradiol release from a ‘core’ designed vaginal ring (Estring®) and furthermore, to establish the in vivo concentration-time course of oestradiol, oestrone and total oestrone (unconjugated plus conjugated) in consecutive applications of such an oestradiol-containing vaginal ring in postmenopausal women. Results indicate that the controlled release design of Estring® produces stable, low systemic plasma concentrations of oestradiol and has an extended time period of release.