VOROZOLE (R83842) IN THE TREATMENT OF POSTMENOPAUSAL ADVANCED BREAST-CANCER - RELATIONSHIP OF SERUM LEVELS OF VOROZOLE AND CLINICAL-RESULTS(A STUDY OF THE EORTC BREAST-CANCER COOPERATIVE GROUP)

The new non-steroidal aromatase inhibitor vorozole (R83842) was admini stered orally at a single daily dose of 2.5 mg to 27 postmenopausal wo men with advanced breast cancer in a phase II trial as second-line end ocrine treatment. The observed objective response rate of 30% and good tolerability of the drug confirm other recent reports. Endocrine dete rminations during 6 months of treatment demonstrated reduction of seru m estrogens: estrone sulfate by more than 60%, estrone by 30-40%, but estradiol by only 10-20%. The ratios of serum androstenedione/estrone and testosterone/estradiol increased significantly, consistent with th e inhibition of peripheral aromatase activity. Levels of progesterone, 17-alpha-hydroxyprogesterone, cortisol, dehydroepiandrosterone sulfat e, androstenedione and aldosterone remained normal, indicating no inte rference with adrenocortical steroid synthesis. A general lack of corr elation between the observed serum concentrations of vorozole and its effect on hormone serum levels or clinical response was found. This su ggests that the determination of such serum levels gives a poor impres sion of the unambiguous anti-tumor activity of vorozole which may well have its main effect with the tumor tissue itself. The present result s are in support of aromatase inhibition, but the possibility of an ad ditional effect on the sulfation of estrogens merits further investiga tion. [(C) 1998 Lippincott-Raven Publishers.].