ANTIPROLIFERATIVE ACTIVITY OF CASODEX (ICI-176.334) IN HORMONE-DEPENDENT TUMORS

MAUCHER, A and VONANGERER, E (1993) ANTIPROLIFERATIVE ACTIVITY OF CASODEX (ICI-176.334) IN HORMONE-DEPENDENT TUMORS. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 119 (11). pp. 669-674. ISSN 0171-5216,

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Abstract

The nonsteroidal antiandrogen casodex has been described as a peripherally selective drug for the treatment of prostatic cancer. In this study we determined its activity in various models of hormone-dependent malignancies including those of the prostate and the breast. Analysis of endocrine effects in rats after 15 days of treatment revealed a strong reduction of the weights of prostates and seminal vesicles and a significant rise of testosterone serum levels as a result of the interference with central feedback mechanisms. The growth of androgen-sensitive human LNCaP/FGC prostate cancer cells was strongly inhibited by casodex. Unlike hydroxyflutamide, casodex was also active in hormone-depleted medium. The inhibitory effect was overcome by addition of testosterone propionate, which indicates an androgen-receptor-mediated mode of action. In rats bearing Dunning R3327-G prostate carcinomas casodex exerted a strong antitumour effect at the beginning of therapy. However, after 4 weeks of treatment tumours resumed growth whereas diethylstilboestrol-treated tumours remained static. In MXT-M3.2 mouse mammary tumours with significant quantities of androgen receptors casodex was also effective in inhibiting tumour growth. After 6 weeks of treatment, tumour weights were reduced by 69% whereas uterine weights were significantly increased, possibly because of a progestin-like activity of the drug. Casodex is very active in various models of hormone-dependent carcinomas. However, the limited duration of action in prostatic tumours and the incomplete growth inhibition in mammary tumours suggest that it should be used only combination with other endocrine therapies.

Item Type: Article
Uncontrolled Keywords: PERIPHERALLY SELECTIVE ANTIANDROGEN; STEROID BINDING CHARACTERISTICS; RECEPTOR GENE-EXPRESSION; BREAST-CANCER CELLS; ANDROGEN RECEPTOR; NONSTEROIDAL ANTIANDROGENS; PROSTATE CARCINOMA; LINE LNCAP; RAT; TUMORS; NONSTEROIDAL ANTIANDROGEN; LNCAP PROSTATE CARCINOMA CELLS; DUNNING R3327-G TUMOR; MXT MOUSE MAMMARY TUMOR
Depositing User: Dr. Gernot Deinzer
Last Modified: 19 Oct 2022 08:42
URI: https://pred.uni-regensburg.de/id/eprint/53804

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