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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).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.

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

Adjusted mean values (back-transformed) of serum androgens at baseline and week 12 in mixed-effect model, with the androgen level (after log transformation) regressed on treatment, visit and interaction between treatment and visit. Bars represent 95% confidence intervals. P-values for the adjusted mean difference for testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) were 0.7322, 0.8432 and 0.3904 at baseline and <0.0001 for all androgens at week 12.
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fig2: Adjusted mean values (back-transformed) of serum androgens at baseline and week 12 in mixed-effect model, with the androgen level (after log transformation) regressed on treatment, visit and interaction between treatment and visit. Bars represent 95% confidence intervals. P-values for the adjusted mean difference for testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) were 0.7322, 0.8432 and 0.3904 at baseline and <0.0001 for all androgens at week 12.

Mentions: The mean androgen levels declined in both treatment arms, and treatment with abiraterone acetate plus prednisone significantly reduced the mean serum androgen levels from baseline to week 12 compared with prednisone alone (Table 1 and Figure 1). The mean serum testosterone was reduced by 90% in the abiraterone acetate plus prednisone arm compared with 49% in the prednisone arm (P<0.0001; Figure 1a); serum androstenedione was reduced by 92% versus 20%, respectively (P=0.0003; Figure 1b); and serum DHEAS was reduced by 86% versus 48%, respectively (P=0.0007; Figure 1c). Comparable results were observed with back-transformed adjusted means in serum androgens estimated in a mixed-effects model (Figure 2).


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)

Adjusted mean values (back-transformed) of serum androgens at baseline and week 12 in mixed-effect model, with the androgen level (after log transformation) regressed on treatment, visit and interaction between treatment and visit. Bars represent 95% confidence intervals. P-values for the adjusted mean difference for testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) were 0.7322, 0.8432 and 0.3904 at baseline and <0.0001 for all androgens at week 12.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Adjusted mean values (back-transformed) of serum androgens at baseline and week 12 in mixed-effect model, with the androgen level (after log transformation) regressed on treatment, visit and interaction between treatment and visit. Bars represent 95% confidence intervals. P-values for the adjusted mean difference for testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) were 0.7322, 0.8432 and 0.3904 at baseline and <0.0001 for all androgens at week 12.
Mentions: The mean androgen levels declined in both treatment arms, and treatment with abiraterone acetate plus prednisone significantly reduced the mean serum androgen levels from baseline to week 12 compared with prednisone alone (Table 1 and Figure 1). The mean serum testosterone was reduced by 90% in the abiraterone acetate plus prednisone arm compared with 49% in the prednisone arm (P<0.0001; Figure 1a); serum androstenedione was reduced by 92% versus 20%, respectively (P=0.0003; Figure 1b); and serum DHEAS was reduced by 86% versus 48%, respectively (P=0.0007; Figure 1c). Comparable results were observed with back-transformed adjusted means in serum androgens estimated in a mixed-effects model (Figure 2).

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).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.

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