Eintrag weiter verarbeiten
Endocrine and clinical responses to steroid sulfatase inhibition: Results from the first phase I trial in women with breast cancer
Gespeichert in:
| Zeitschriftentitel: | Journal of Clinical Oncology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Journal of Clinical Oncology, 24, 2006, 18_suppl, S. 580-580 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Clinical Oncology (ASCO)
|
| Schlagwörter: |
| Zusammenfassung: | <jats:p> 580 </jats:p><jats:p> Background: Steroid sulfatase (STS) inhibitors, such as STX64, were developed to block the sulfatase pathway of estrogen formation in postmenopausal (PM) women with ER+ breast cancer. They act by blocking the formation of estrone from estrone sulfate but also inhibit the synthesis of androstenediol (Adiol), a steroid with potent estrogenic properties, which is derived from dehydroepiandrosterone sulfate (DHEAS). Methods: Fourteen PM women with ER+ metastatic breast cancer were recruited for this Phase I trial. All patients had received at least two previous lines of endocrine therapy and all but one had received prior chemotherapy. STX64 was administered orally as an initial test dose (5mg, n=9; 20mg, n=5) followed one week later by 3 two weekly cycles with dosing for 5 days followed by 9 days off treatment for 12–145 days. Blood samples were collected for the assessment of STS activity in peripheral blood lymphocytes and steroid concentrations. For some patients core biopsies of tumor samples were obtained before and during therapy. Results: Almost complete inhibition of peripheral STS (median 98%) and tumor (median 99%) activity was achieved on dosing with STX64. This was associated with significant decreases in the concentrations of estradiol, androstenediol (up to 90%) and unexpectedly, androstenedione (up to 86%). Monitoring the ratios of DHEAS:DHEA (a marker of STS inhibition) in patients receiving extended dosing revealed an inverse relationship between this ratio and serum Adiol concentrations. Three patients with prior adjuvant tamoxifen and aromatase inhibitor therapy showed stable disease for >6 months with a favorable safety profile. Full results will be presented at the meeting. Conclusions: STX64 is a potent, well tolerated STS inhibitor. The unexpected finding that androstenedione levels decreased indicates that peripheral formation, rather than secretion from the adrenal cortex, in the major source of this steroid which is the main substrate for the aromatase. The disease stabilization seen for 4 patients, all of whom had previously progressed on aromatase inhibitor therapy, suggests that STS inhibitors should have considerable therapeutic potential for the treatment of breast cancer. </jats:p><jats:p> [Table: see text] </jats:p> |
|---|---|
| Umfang: | 580-580 |
| ISSN: |
0732-183X
1527-7755 |
| DOI: | 10.1200/jco.2006.24.18_suppl.580 |