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Lessons from the SWITCH trial: changing glucocorticoids in the management of metastatic castration-resistant prostate cancer (mCRPC).

ABSTRACT: Abiraterone acetate plus prednisone is a standard treatment option for mCRPC. The phase II SWITCH trial showed that further prostate-specific antigen (PSA) responses can be obtained in a subset of patients when prednisone was switched to dexamethasone at progression. Here, we discuss the potential underlying mechanisms, including the activation of glucocorticoid receptors (GR) in progressive mCRPC and the implications for clinical practice.

SUBMITTER: Teo MY

PROVIDER: S-EPMC6219496 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Lessons from the SWITCH trial: changing glucocorticoids in the management of metastatic castration-resistant prostate cancer (mCRPC).

Teo Min Yuen MY Scher Howard I HI

British journal of cancer 20181022 9

Abiraterone acetate plus prednisone is a standard treatment option for mCRPC. The phase II SWITCH trial showed that further prostate-specific antigen (PSA) responses can be obtained in a subset of patients when prednisone was switched to dexamethasone at progression. Here, we discuss the potential underlying mechanisms, including the activation of glucocorticoid receptors (GR) in progressive mCRPC and the implications for clinical practice. ...[more]

PMID: 30344307

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Project description:BackgroundMultiple androgens drive prostate cancer progression and higher pre-treatment levels of androgens, even within the castrate range, have been previously shown to be associated with an improved overall survival (OS) in mCRPC. Docetaxel impairs microtubules, has androgen receptor (AR) inhibitory effects and is used in both the castration resistant and sensitive settings, where androgen dynamics may impact outcome. The present analysis evaluates the association of decline in serum androgen levels (Testosterone (T), Androstenedione (A) and DHEA in docetaxel-treated mCRPC patients with OS.MethodsData from 1050 men treated on CALGB 90401 with docetaxel, prednisone and either bevacizumab or placebo were evaluated. Eligibility required progressive mCRPC and no prior chemotherapy. Pre-treatment, 6 week and progression serum assays for T, A and DHEA were performed via tandem Liquid Chromatography-Mass Spectrometry (LC-MS/MS). Changes in T, A and DHEA levels from baseline to 6 weeks were calculated as the ratio of 6-week over baseline. The proportional hazards model was used to assess the prognostic significance of changes in T, A, and DHEA from baseline to 6 weeks in predicting OS adjusting for known prognostic factors.ResultsMedian baseline values for T, A, and, DHEA were 1.0, 13.5, and 8.1 ng/dL respectively while 6 week levels were 0.64, 7.0, and 6.8 ng/dL respectively. Median OS for low testosterone decline is 20.9 months vs 26.3 months for high testosterone decline. In multivariable analysis including known prognostic variables, change in testosterone levels was independently associated with greater OS; the hazard ratio for death with each unit increase in the 6-week/baseline ratio is 1.02 (95% CI = 1.01-1.03, p = 0.001). Decline in A and DHEA were not significant predictors of OS. In multivariable analysis change in the serum changes did not predict PFS however the ratio of T at 6-weeks over baseline was prognostic of ≥50% decline in PSA with an odds ratio of 0.93 (95% CI = 0.85-0.98, p-value = 0.039).ConclusionsDeclines in testosterone during docetaxel treatment is associated with a longer survival, consistent with a favorable prognostic significance of higher serum androgens in the CRPC.

Dataset Information

Lessons from the SWITCH trial: changing glucocorticoids in the management of metastatic castration-resistant prostate cancer (mCRPC).

Publications

Lessons from the SWITCH trial: changing glucocorticoids in the management of metastatic castration-resistant prostate cancer (mCRPC).

Similar Datasets

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