scholarly journals Metastatic Castration-Resistant Prostate Cancer: Two Case Reports of Dramatic Response with Abiraterone Acetate in Patients Heavily Pretreated with Chemotherapy

2013 ◽  
Vol 6 (2) ◽  
pp. 325-330 ◽  
Author(s):  
Laura Dupuy ◽  
Jérôme Long ◽  
Yves Ranchoup
Keyword(s):  
Prostate Cancer ◽  
Case Reports ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Heavily Pretreated

Early abiraterone treatment after surgical castration in in vivo castration resistant prostate cancer (CRPC) tumors in nude mice.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 263-263 ◽  
Author(s):  
Paul Thelen ◽  
Verena Reupke ◽  
Felix Bremmer ◽  
Hubertus Jarry
Keyword(s):  
Prostate Cancer ◽  
Tumor Regression ◽  
Case Reports ◽  
Initial Therapy ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Tumor Bearing ◽  
Castration Resistant ◽  
Tumor Mouse Model

263 Background: ADT is the initial therapy for advanced prostate cancer, and androgen biosynthesis inhibitors (abiraterone-acetate, AA) reveal clinical survival benefit for CRPC. On CRPC progression, therapy sequencing towards androgen receptor (AR) antagonism is applied and AA withdrawal / re-challenge strategies (+AA-AA+AA) succeeded in several case reports. Here we established a VCaP-tumor mouse model for a +AA-AA+AA-sequence and external testosterone-boosts (+AA[-AA+T]+AA). Methods: 20 tumor bearing mice (from 106 VCaP in Matrigel) received surgical ADT and then +AA-AA+AA, (AA intraperitoneal 70mg/kg, daily [Janssen-Cilag]), or +AA[-AA+T]+AA (+0.6 µl/kg Nebido [250mg testosterone-undecaonate/ml, Jenapharm]). Tumor growth was monitored with calipers. When tumors grew > 200 mm3, animals were castrated and treatment-sequences began when CRPC growth became evident (n = 15) or early one week after castration (n = 5). Expression analyses were performed with Experion, CSX-96 and ChemiDoc, chemicals, software (BioRad). Steroids were quantified by Dept. Clin. Chemistry. Results: 20 tumor-bearing mice received ADT. To interfere with ADT failure for 15 mice +AA-AA+AA (n = 7) or +AA[-AA+T]+AA (n = 8) commenced when tumors doubled within two weeks. Animals benefited a reduction of up to 210 mm3 receiving +AA-AA+AA, whereas a T-Boost in +AA[-AA+T]+AA revealed a loss of solid tumor mass as mean 42% (+/-21%) liquid effusion. No complete remission was observed, tumors > 1 cm3 were considered dead-of-disease (DOD). Another group (n = 5) was AA-treated one week after castration. There +AA-AA+AA and +AA[-AA+T]+AA resulted for one animal in DOD, however tumors of up to 990 mm3 underwent complete remissions (n = 4) and tumor-free untreated survival. AA-withdrawal is associated with progesterone decrease and DHEA increase. AR (+ AR-Vs) decreases to 95% expression immediately after -AA and to 39% (no AR-Vs) upon +T. Conclusions: Therapy sequences with AA-withdrawal/rechallenge may lead to tumor regression and complete tumor-free survival. Concomitant with tumor regression upon AA-withdrawal, AR overexpression is reduced, which may be boosted with testosterone supplementation.

A multicenter phase II study of abiraterone acetate (AA) in docetaxel pretreated castration-resistant prostate cancer (CRPC) patients (pts)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5047-5047
Author(s):  
A. H. Reid ◽  
G. Attard ◽  
D. Danila ◽  
C. J. Ryan ◽  
E. Thompson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Patient Demographics ◽  
Castration Resistant ◽  
Heavily Pretreated ◽  
Key Enzyme ◽  
Psa Response ◽  
Docetaxel Chemotherapy

5047 Background: Despite castration, androgens remain critical to prostate cancer. Abiraterone acetate (AA) specifically and irreversibly inhibits CYP17, a key enzyme in androgen biosynthesis. Methods: 47 CRPC pts who had failed androgen deprivation therapy and had prior docetaxel chemotherapy received AA orally (1000mg QD) in 28 day cycles. Low dose glucocorticoids were allowed. Results: Patient demographics in table . Total maximal PSA declines with AA at any point on study of ≥30%, ≥50%, and ≥ 90% were observed in 32 (69%), 24 (51%) and 7 (15%) pts respectively. A similar trend in PSA response was seen at wk 12. 35 pts were evaluable by RECIST; 6 (17%) pts had a partial response and 23 (66%) pts had stable disease. 23% of pts showed ECOG improvement (PS 1 to 0 in 10 pts, PS 2 to 1 in 1 pt); 53% of pts maintained PS. Median duration on treatment was 167 days (95% CI 130–201). 17 pts received >6 cycles of AA; 8 pts received ≥ 12 cycles. Toxicities related to mineralocorticoid excess were mainly grade 1–2 (hypokalemia 51%; HTN 17%; edema 13%) and were treated with eplerenone or corticosteroids. Conclusions: AA has anti-tumor activity in these heavily pretreated pts, as evidenced by sustained PSA declines, improvement in PS and RECIST responses. A phase III trial assessing the efficacy and safety of AA and prednisone in CRPC pts who have failed docetaxel chemotherapy is underway. [Table: see text] [Table: see text]

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