Association between levels of hormones implied in steroid biosynthesis pathway and activity of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): An exploratory analysis in Journal of Clinical Oncology
2015
AOU San Luigi di Orbassano
Tipo pubblicazione
Conference Abstract
Autori/Collaboratori (7)Vedi tutti...
Tucci M
Vignani F
Bertaglia V
et alii...
Abstract
Background: AA inhibits 17?-hydroxylase and C17,20-lyase, blocking androgen biosynthesis. It is approved for treatment in patients with mCRPC. Aim of this analysis was to describe changes in hormonal levels determined by AA, and to explore the association between levels (both baseline and changes) of hormones implied in steroid biosynthesis pathway and drug activity. Methods: Pts receiving AA 1000 mg daily + prednisone 5 mg twice daily for mCRPC, after failure of docetaxel, were included in this mono-institutional study. Serum levels of progesterone, 17OH-progesterone, cortisol, DHEA sulfate, androstenedione, testosterone, sex hormone binding globulin, aldosterone, plasma renin activity, ACTH and cholesterol, were determined at baseline and every 12 wks, until progression. Hormonal levels at baseline vs subsequent samples were compared by Wilcoxon matched-pairs test. Association between hormones and treatment activity (?50% PSA reduction) was tested (1) comparing baseline levels of responders vs non- responders; (2) comparing progression-free survival (PFS) of pts with baseline low vs high values of each hormone; (3) comparing levels after 12 wks of responders vs non- responders, adjusted by baseline levels. Results: 49 pts were included in the analysis (median age 70, ECOG PS 0/1/2 61%/33%/6%, median baseline PSA 116.95). 82% were metastatic to bone. PSA reduction was obtained in 26 pts (53.1%). Median PFS was 10.2 months. Baseline levels of all hormones were not statistically different between responders and non-responders. For all hormones, difference in PFS of pts with low baseline values vs pts with high baseline values was not statistically significant. Several hormones showed significant and sustained changes vs baseline, but all significant changes were similar between responders and non-responders. Conclusions: Although limited by low statistical power, our exploratory analysis does not suggest a significant association between baseline levels of
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Keywords
American; castration resistant prostate cancer; human; patient; steroidogenesis; prasterone; corticotropin; cholesterol; aldosterone; prasterone sulfate; docetaxel; prednisone; sex hormone binding globulin; testosterone; oxygenase; hydrocortisone; androstenedione; progesterone; steroid 17alpha monooxygenase; hormone; abiraterone acetate; society; oncology; blood level; androgen synthesis; drug activity; plasma renin activity; progression free survival; bone; electrocorticography;