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Androgen dynamics and serum PSA in patients treated with abiraterone acetate.

Ryan CJ, Peng W, Kheoh T, Welkowsky E, Haqq CM, Chandler DW, Scher HI, Molina A - Prostate Cancer Prostatic Dis. (2014)

Bottom Line: Serum testosterone, androstenedione and dehydroepiandrosterone sulfate from baseline to week 12 were measured by novel ultrasensitive two-dimensional liquid chromatography coupled to tandem mass spectrometry assays in a subset of subjects in each arm (abiraterone plus prednisone, n=80; prednisone, n=38).A significantly greater reduction in serum androgens was observed with abiraterone plus prednisone versus prednisone (all P < or = 0.0003), reaching undetectable levels for testosterone (47.2% versus 0%, respectively).Abiraterone plus prednisone significantly reduced serum androgens, as measured by ultrasensitive assays and was generally associated with PSA response.

View Article: PubMed Central - PubMed

Affiliation: University of California San Francisco, San Francisco, CA, USA.

ABSTRACT

Background: We analyzed the potential of abiraterone acetate (henceforth abiraterone) to reduce androgen levels below lower limits of quantification (LLOQ) and explored the association with changes in PSA decline in metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods: COU-AA-301 is a 2:1 randomized, double-blind, placebo-controlled study comparing abiraterone (1000 mg q.d.) plus low-dose prednisone (5 mg b.i.d.) with placebo plus prednisone in mCRPC patients post docetaxel. Serum testosterone, androstenedione and dehydroepiandrosterone sulfate from baseline to week 12 were measured by novel ultrasensitive two-dimensional liquid chromatography coupled to tandem mass spectrometry assays in a subset of subjects in each arm (abiraterone plus prednisone, n=80; prednisone, n=38). The association between PSA response (< or =50% baseline) and undetectable androgens (week 12 androgen level below LLOQ) was analyzed using logistic regression.

Results: A significantly greater reduction in serum androgens was observed with abiraterone plus prednisone versus prednisone (all P < or = 0.0003), reaching undetectable levels for testosterone (47.2% versus 0%, respectively). A positive association was observed between achieving undetectable serum androgens and PSA decline (testosterone: odds ratio=1.54; 95% confidence interval: 0.546-4.347). Reduction of androgens to undetectable levels did not occur in all patients achieving a PSA response, and a PSA response did not occur in all patients achieving undetectable androgen levels.

Conclusions: Abiraterone plus prednisone significantly reduced serum androgens, as measured by ultrasensitive assays and was generally associated with PSA response. However, androgen decline did not uniformly predict PSA decline suggesting ligand-independent or other mechanisms for mCRPC progression.

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Related in: MedlinePlus

Waterfall plots for maximal PSA change in patients who did and did not achieve undetectable serum testosterone levels. If patient had decreased PSA value on at least one post-baseline visit, maximal PSA change=maximal PSA decrease. If patient had no decreased PSA value on any post-baseline visits, maximal PSA change=maximal PSA increase. *Truncated values.
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fig3: Waterfall plots for maximal PSA change in patients who did and did not achieve undetectable serum testosterone levels. If patient had decreased PSA value on at least one post-baseline visit, maximal PSA change=maximal PSA decrease. If patient had no decreased PSA value on any post-baseline visits, maximal PSA change=maximal PSA increase. *Truncated values.

Mentions: Logistic regression analysis demonstrates that the reduction of androgens to undetectable levels increases the odds of achieving a ⩾50% PSA decline (Table 4). The strongest association was observed for androstenedione, for which patients who achieved undetectable serum levels had a threefold greater likelihood of PSA response compared with those who did not (adjusted OR=3.06; 95% confidence interval: 0.975–9.604). The OR relating undetectable serum testosterone with PSA response was 1.54 (95% confidence interval: 0.546–4.347). However, achieving undetectable serum testosterone was not required for a PSA response with abiraterone acetate (Figure 3), as 15 of 109 patients (14%) experienced a ⩾50% decline in PSA without achieving undetectable testosterone. Similar trends were observed for serum androstenedione and DHEAS (data not shown).


Androgen dynamics and serum PSA in patients treated with abiraterone acetate.

Ryan CJ, Peng W, Kheoh T, Welkowsky E, Haqq CM, Chandler DW, Scher HI, Molina A - Prostate Cancer Prostatic Dis. (2014)

Waterfall plots for maximal PSA change in patients who did and did not achieve undetectable serum testosterone levels. If patient had decreased PSA value on at least one post-baseline visit, maximal PSA change=maximal PSA decrease. If patient had no decreased PSA value on any post-baseline visits, maximal PSA change=maximal PSA increase. *Truncated values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4020277&req=5

fig3: Waterfall plots for maximal PSA change in patients who did and did not achieve undetectable serum testosterone levels. If patient had decreased PSA value on at least one post-baseline visit, maximal PSA change=maximal PSA decrease. If patient had no decreased PSA value on any post-baseline visits, maximal PSA change=maximal PSA increase. *Truncated values.
Mentions: Logistic regression analysis demonstrates that the reduction of androgens to undetectable levels increases the odds of achieving a ⩾50% PSA decline (Table 4). The strongest association was observed for androstenedione, for which patients who achieved undetectable serum levels had a threefold greater likelihood of PSA response compared with those who did not (adjusted OR=3.06; 95% confidence interval: 0.975–9.604). The OR relating undetectable serum testosterone with PSA response was 1.54 (95% confidence interval: 0.546–4.347). However, achieving undetectable serum testosterone was not required for a PSA response with abiraterone acetate (Figure 3), as 15 of 109 patients (14%) experienced a ⩾50% decline in PSA without achieving undetectable testosterone. Similar trends were observed for serum androstenedione and DHEAS (data not shown).

Bottom Line: Serum testosterone, androstenedione and dehydroepiandrosterone sulfate from baseline to week 12 were measured by novel ultrasensitive two-dimensional liquid chromatography coupled to tandem mass spectrometry assays in a subset of subjects in each arm (abiraterone plus prednisone, n=80; prednisone, n=38).A significantly greater reduction in serum androgens was observed with abiraterone plus prednisone versus prednisone (all P < or = 0.0003), reaching undetectable levels for testosterone (47.2% versus 0%, respectively).Abiraterone plus prednisone significantly reduced serum androgens, as measured by ultrasensitive assays and was generally associated with PSA response.

View Article: PubMed Central - PubMed

Affiliation: University of California San Francisco, San Francisco, CA, USA.

ABSTRACT

Background: We analyzed the potential of abiraterone acetate (henceforth abiraterone) to reduce androgen levels below lower limits of quantification (LLOQ) and explored the association with changes in PSA decline in metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods: COU-AA-301 is a 2:1 randomized, double-blind, placebo-controlled study comparing abiraterone (1000 mg q.d.) plus low-dose prednisone (5 mg b.i.d.) with placebo plus prednisone in mCRPC patients post docetaxel. Serum testosterone, androstenedione and dehydroepiandrosterone sulfate from baseline to week 12 were measured by novel ultrasensitive two-dimensional liquid chromatography coupled to tandem mass spectrometry assays in a subset of subjects in each arm (abiraterone plus prednisone, n=80; prednisone, n=38). The association between PSA response (< or =50% baseline) and undetectable androgens (week 12 androgen level below LLOQ) was analyzed using logistic regression.

Results: A significantly greater reduction in serum androgens was observed with abiraterone plus prednisone versus prednisone (all P < or = 0.0003), reaching undetectable levels for testosterone (47.2% versus 0%, respectively). A positive association was observed between achieving undetectable serum androgens and PSA decline (testosterone: odds ratio=1.54; 95% confidence interval: 0.546-4.347). Reduction of androgens to undetectable levels did not occur in all patients achieving a PSA response, and a PSA response did not occur in all patients achieving undetectable androgen levels.

Conclusions: Abiraterone plus prednisone significantly reduced serum androgens, as measured by ultrasensitive assays and was generally associated with PSA response. However, androgen decline did not uniformly predict PSA decline suggesting ligand-independent or other mechanisms for mCRPC progression.

Show MeSH
Related in: MedlinePlus