et al., 1991). Breast cancer studies may unveil original PR-dependent control mechanisms of the cell cycle—in particular, hormone-independent, receptor-dependent or -independent effects (as already suggested for tamoxifen). In other words, just as for antiestrogens (Bardon et al., 1987), there may be receptor-mediated antihormonal cytostatic activity, receptor-mediated cytotoxic activity (nonantihormonal), and nonspecific cytotoxic activity of RU 486 and parent drugs.

The growth of other cancers may be decreased by RU 486 treatment. It may act via the PR as in the case of androgen-insensitive R3327HI rat prostatic carcinoma (Mobbs and Johnson, 1991).

Meningioma

Meningiomas are common tumors, generally benign and slow growing, that can threaten brain function—or even life—if they are not surgically removed. More frequent in women, meningioma growth is accelerated during pregnancy. Most meningiomas contain PR (and often little or no ER), and it has been suggested that progesterone has either a permissive or a facilitating effect on their evolution, or possibly both (Magdalenat et al., 1982; Blankestein et al., 1983; Haak et al., 1990; Grunberg et al., 1991; Lamberts, 1992a,b,c). Administration of RU 486 over several months (usually 200 mg/day) has essentially been well tolerated; even the expected side effects reproducing the features of the familial syndrome of cortisol resistance have been observed—that is, relative glucocorticosteroid insufficiency in the presence of high blood cortisol with arterial pressure is maintained because aldosterone secretion is increased.

The treatment should be restricted to unresectable meningiomas. The spontaneous variety of evolution of these tumors makes a definitive evaluation of the beneficial effects very difficult, even though definite, sometimes spectacular improvement has been observed in about one-third of available reports. Instead of RU 486, an antiprogesterone without antiglucocorticosteroid activity would be welcomed. Conversely, there are gliomas whose growth is sensitive to glucocorticosteroid that may benefit from antiglucocorticosteroid compounds (Langeveld et al., 1992; Pinski et al., 1993).

ANTIGLUCOCORTICOSTEROID EFFECTS

While demonstrating antiglucocorticosteroid activity in vitro (Philibert et al., 1981; Jung-Testas and Baulieu, 1983), RU 486 is the first powerful antiglucocorticosteroid whose activity has also been demonstrated in vivo (Bertagna et al., 1984; Gaillard et al., 1984). As one might predict, given the elimination of the negative feedback control of cortisol on ACTH, RU 486 leads to increased ACTH and cortisol secretion. This



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