Time for revival of estrogens in the treatment of advanced prostatic carcinoma? Pharmacokinetics, and endocrine and clinical effects, of a parenteral estrogen regimen

✍ Scribed by Henriksson, Peter; Carlstr�m, Kjell; Pousette, �ke; Gunnarsson, P.O.; Johansson, C.J.; Eriksson, Birgitta; Altersg�rd-Brorsson, Ann Kristin; Nordle, �rjan; Stege, Reinhard

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 235 KB
• Volume: 40
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(19990701)40:2<76::aid-pros2>3.0.co;2-q

✦ Synopsis

BACKGROUND.

The present pilot study tested the clinical performance of a new pharmacokinetically guided dosing regimen of parenteral estrogen in patients with advanced prostatic carcinoma. The aim was to accelerate endocrine effects and to avoid cardiovascular side effects. METHODS. Seventeen patients were randomized to intramuscular injections of 240 mg polyestradiol phosphate (PEP) every second week for the first 8 weeks (five doses), followed by a maintenance dose of 240 mg every month; and 16 patients were randomized to bilateral orchidectomy. The estrogen dosing was calculated by pharmacokinetic modelling to achieve a rapid increase in serum estradiol and thereby a fast decrease in testosterone. RESULTS. The predicted increment in serum estrogen was achieved, together with a subsequent decrease in testosterone in the PEP group. In addition, there were no signs of an increased cardiovascular morbidity. This was probably due to a minimal estrogenic influence on the liver and was reflected by unchanged levels of coagulation factor VII. Clinical effects, during the first 2 years of treatment, were similar in the two treatment arms, with 12 patients in the orchidectomy group and 14 patients in the PEP group responding to treatment. CONCLUSIONS. The present parenteral regimen is an efficient and time-saving estrogen regimen with a favorable side-effect profile. PEP seems to offer a potential for revival of the most cost-effective endocrine treatment of cancer of the prostate, i.e., estrogen.