2017
DOI: 10.1158/1078-0432.ccr-16-0987
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A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer

Abstract: Purpose Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride. Experimental Design Eligible metastatic CRPC patients underwent a baseline metastasis biopsy. Patients received abiraterone and prednisone for two 4-week cycles. After this time, high-dose du… Show more

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Cited by 31 publications
(35 citation statements)
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“…The reported values in subjects with BPH or PC appear to be similar to those in healthy controls (1.5-2.5 nM) (Hammond et al 1977, 1978, Belanger et al 1994. Elevated pregnenolone levels were observed in abiraterone-treated CRPC patients (16.3 nM, IQR 9.85-27.77 nM) using LC-MS/MS, and it was also noted that patients with high serum abiraterone levels (>35 ng/mL) had higher pregnenolone levels than patients with low abiraterone concentrations (McKay et al 2017). This can be explained by impaired conversion of pregnenolone to 17OH-pregnenolone because of CYP17A1 inhibition by abiraterone, resulting in the accumulation of the former steroid.…”
Section: Pregnenolone and Progesteronementioning
confidence: 64%
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“…The reported values in subjects with BPH or PC appear to be similar to those in healthy controls (1.5-2.5 nM) (Hammond et al 1977, 1978, Belanger et al 1994. Elevated pregnenolone levels were observed in abiraterone-treated CRPC patients (16.3 nM, IQR 9.85-27.77 nM) using LC-MS/MS, and it was also noted that patients with high serum abiraterone levels (>35 ng/mL) had higher pregnenolone levels than patients with low abiraterone concentrations (McKay et al 2017). This can be explained by impaired conversion of pregnenolone to 17OH-pregnenolone because of CYP17A1 inhibition by abiraterone, resulting in the accumulation of the former steroid.…”
Section: Pregnenolone and Progesteronementioning
confidence: 64%
“…In one trial, median serum testosterone in CRPC patients declined from 0.35 nM at baseline to 0.02 nM after 12 weeks treatment with 1000 mg abiraterone and 5 mg prednisone daily (McKay et al 2017). This is lower than the in vitro activation thresholds observed in literature, although intracellular levels may differ (Sonneveld et al 2005, Campana et al 2016.…”
Section: :11mentioning
confidence: 84%
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