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Breast Unit [T. J. I., I. E. S., J. A.] and Department of Biochemistry [T. J. I., D. A. S., M. D.], Royal Marsden Hospital, London SW3 6JJ, England, and Ciba-Geigy, Basel, Switzerland [P. F. T.]
2 To whom requests for reprints should be addressed.
A phase I study was performed of CGS 20267, an oral nonsteroidal, highly potent, and selective aromatase inhibitor, in 21 postmenopausal patients with advanced breast cancer. The patients were recruited in 3 successive groups of 7, receiving 0.1, 0.5, and 2.5 mg p.o./day, respectively. All patients had received at least one prior endocrine treatment (range, 1–4), and six patients had received prior chemotherapy. The treatment was very well tolerated, and no toxicity was seen at any of the three doses. There was a statistically significant suppression of estradiol (E2) and estrone (E1) levels by 74% and 79% from baseline levels, respectively (P < 0.0001). Suppression occurred in all three patient groups, with many patients having serum concentrations of estradiol and estrone, which were below the limit of detection of the assays (3 and 10 pM, respectively), which corresponds to a maximum measurable estrogen suppression of 86%. CGS 20267 had no significant effect on serum levels of follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, Cortisol, 17
-hydroxyprogesterone, androstenedione, and aldosterone. Seven (33%, 95% confidence interval, 15–57%) of the 21 patients have responded to treatment (one complete remission, 6 partial remissions according to criteria of the Union Internationale contre le Cancer), and 6 are still responding to CGS 20267 (duration of response; 4+, 6+, 6+, 9+, 9, 12+, and 12+ months). Five have had stable disease for more than 3 months, and 9 had progressive disease.
These results suggest that CGS 20267 is a very potent and specific aromatase inhibitor, and phase II studies are now required to confirm its clinical efficacy.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 7/13/92. Accepted 11/ 2/92.
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