ArticleProstate cancer and prostatic diseases2020
Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC).
Article in Prostate cancer and prostatic diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Impact of adding carboplatin to docetaxel chemotherapy on testosterone levels and treatment outcomes in metastatic docetaxel-resistant prostate cancer.Scientific reports · 2025Article
- Androgen production, uptake, and conversion (APUC) genes define prostate cancer patients with distinct clinical outcomes.JCI insight · 2024Article
- A Modified Net Reclassification Improvement Statistic.Journal of statistical planning and inference · 2023Article
- LncFALEC recruits ART5/PARP1 and promotes castration-resistant prostate cancer through enhancing PARP1-meditated self PARylation.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients.Scientific reports · 2021Article
- Molecular Profiling of Docetaxel-Resistant Prostate Cancer Cells Identifies Multiple Mechanisms of Therapeutic Resistance.Cancers · 2021Article
- IL-23 and PSMA-targeted duo-CAR T cells in Prostate Cancer Eradication in a preclinical model.Journal of translational medicine · 2020Article
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9 authors at 6 institutions in 1 country.
Funding
Abstract
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.
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