In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 4549-4549
Kurzfassung:
4549 Background: Ortl is an investigational, oral, non-steroidal selective 17,20-lyase inhibitor that suppresses androgen production. Ortl affects cortisol synthesis less than similar agents due to limited inhibition of 17α-hydroxylase, and may permit steroid-free dosing. Ortl 300 mg BID was examined in patients (pts) with nmCRPC and rising PSA. Methods: Eligible pts had nmCRPC with PSA ≥2 ng/mL (PSA ≥8 ng/mL if doubling time 〉 8 mo), and surgical/medical castration, with testosterone (T) 〈 50 ng/dL. Prior chemotherapy, ketoconazole, or concomitant corticosteroids were excluded. Starting dose of ortl was 300 mg BID and continued until PSA progression, metastases, or unacceptable toxicity. The primary endpoint was the percentage of pts with PSA ≤0.2 ng/mL after 3 mo. Secondary endpoints included safety, PSA kinetics, time to metastases, changes in endocrine markers and circulating tumor cells (CTCs). Results: 39 pts were enrolled with baseline demographics including median age 71 y, ECOG PS ≤1, median PSA 12.1 ng/mL (range 2.6-67.8), T 7.9 ng/dL (1.4–17.3), and ACTH 19 ng/L (n=33; 0-47); 3 pts had dose reduction due to adverse events (AEs). Gr ≥3 AEs occurred in 16 pts (drug-related in 14); Gr ≥3 AEs ≥5% were dyspnea (8%), hypertension (13%), fatigue, hypokalemia, pneumonitis (5% ea). 7 pts (18%) had serious AEs; most common was pneumonitis (2=Gr 3, 1=Gr 2). 8 pts discontinued due to AEs; 2 pts required corticosteroids. At 3 mo, 6 pts (16%) achieved PSA ≤0.2 ng/mL; PSA50 and PSA90 rates were 76% and 32%, respectively; median PSA declined by 83% (n=34); median T declined by 89% to 0.78 ng/dL (n=31), and median ACTH increased by 171% to 43 ng/L; median cortisol declined by 21%. At 6 mo, PSA50 and PSA90 rates were 45% and 21%, respectively. Median time to PSA progression was 14.8 mo. 17 pts (44%) were on treatment 〉 6 mo. Of 37 pts with baseline CTC/7.5 mL assessed, only 1 had CTC ≥5 and converted to 〈 5; 6 had 1–4 CTCs at baseline, none converted to ≥5 during treatment. Conclusions: Ortl without steroids produces marked and durable declines in T and PSA, has manageable toxicities, and is feasible in men with nmCRPC.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.4549
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2012
ZDB Id:
2005181-5
