Skip to main content

Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC).

Publication ,  Journal Article
Ryan, CJ; Dutta, S; Kelly, WK; Russell, C; Small, EJ; Morris, MJ; Taplin, M-E; Halabi, S ...
Published in: Prostate Cancer Prostatic Dis
March 2020

BACKGROUND: Multiple 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. METHODS: Data 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. RESULTS: Median 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). CONCLUSIONS: Declines in testosterone during docetaxel treatment is associated with a longer survival, consistent with a favorable prognostic significance of higher serum androgens in the CRPC.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Prostate Cancer Prostatic Dis

DOI

EISSN

1476-5608

Publication Date

March 2020

Volume

23

Issue

1

Start / End Page

66 / 73

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Treatment Outcome
  • Sensitivity and Specificity
  • Prostatic Neoplasms, Castration-Resistant
  • Neoplasm Staging
  • Neoplasm Metastasis
  • Male
  • Humans
  • Docetaxel
  • Biomarkers
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ryan, C. J., Dutta, S., Kelly, W. K., Russell, C., Small, E. J., Morris, M. J., … From The Alliance for Clinical Trials in Oncology Genitourinary Committee, . (2020). Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC). Prostate Cancer Prostatic Dis, 23(1), 66–73. https://doi.org/10.1038/s41391-019-0152-3
Ryan, Charles J., Sandipan Dutta, William K. Kelly, Carly Russell, Eric J. Small, Michael J. Morris, Mary-Ellen Taplin, Susan Halabi, and Susan From The Alliance for Clinical Trials in Oncology Genitourinary Committee. “Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC).Prostate Cancer Prostatic Dis 23, no. 1 (March 2020): 66–73. https://doi.org/10.1038/s41391-019-0152-3.
Ryan CJ, Dutta S, Kelly WK, Russell C, Small EJ, Morris MJ, et al. Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC). Prostate Cancer Prostatic Dis. 2020 Mar;23(1):66–73.
Ryan, Charles J., et al. “Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC).Prostate Cancer Prostatic Dis, vol. 23, no. 1, Mar. 2020, pp. 66–73. Pubmed, doi:10.1038/s41391-019-0152-3.
Ryan CJ, Dutta S, Kelly WK, Russell C, Small EJ, Morris MJ, Taplin M-E, Halabi S, From The Alliance for Clinical Trials in Oncology Genitourinary Committee. Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC). Prostate Cancer Prostatic Dis. 2020 Mar;23(1):66–73.

Published In

Prostate Cancer Prostatic Dis

DOI

EISSN

1476-5608

Publication Date

March 2020

Volume

23

Issue

1

Start / End Page

66 / 73

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Treatment Outcome
  • Sensitivity and Specificity
  • Prostatic Neoplasms, Castration-Resistant
  • Neoplasm Staging
  • Neoplasm Metastasis
  • Male
  • Humans
  • Docetaxel
  • Biomarkers