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Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer: potential for rapid monitoring of treatment responses

Ulmert, David LU ; Vickers, Andrew J.; Scher, Howard I.; Becker, Charlotte LU ; Iversen, Peter; Frankel, David; Jensen, Jens-Kristian; Olesen, Tine Kold and Lilja, Hans LU (2012) In Clinical Chemistry and Laboratory Medicine 50(11). p.1993-1998
Abstract
Background: The utility of conventional prostate-specifi c antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase 2 (hK2) are eliminated more rapidly after radical prostatectomy. In contrast, all three markers have similarly slow elimination rates after castration induced by gonadotropin-releasing hormone (GnRH) agonists, possibly due to the slow onset of castration. Therefore, we assessed elimination rates of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon (R)), a novel GnRH antagonist. Methods: This study... (More)
Background: The utility of conventional prostate-specifi c antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase 2 (hK2) are eliminated more rapidly after radical prostatectomy. In contrast, all three markers have similarly slow elimination rates after castration induced by gonadotropin-releasing hormone (GnRH) agonists, possibly due to the slow onset of castration. Therefore, we assessed elimination rates of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon (R)), a novel GnRH antagonist. Methods: This study included 24 patients treated with degarelix. Blood was taken at 1, 3, 7, 14, 21 and 28 days after injection of degarelix. Free and total PSA were measured with a commercial dual-label assay, and with inhouse research assays of intact PSA and hK2. Results: Median (interquartile range, IQR) tPSA at baseline was 23.4 (15.8, 59.8). Twenty-two patients (92%) reached castrate levels of testosterone within 24 h of degarelix initiation, and all patients did so within 72 h. All kallikrein forms declined in an exponential fashion after degarelix administration. The median time to 50% reduction in biomarker level was 8-9 days for tPSA or complexed PSA vs. 2-4 days for hK2, iPSA and fPSA. The percentage eliminated at day 3 and day 7 was significantly higher for hK2, iPSA and fPSA than for tPSA (all p<0.02), while tPSA and complexed PSA were similar. Conclusions: The rapid decline of fPSA, iPSA and hK2 after fast induction of castration with degarelix is similar to that reported after prostatectomy and offers a novel, informative method to monitor rapid onset of therapeutic action targeting signaling of the androgen receptor. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
androgen deprivation therapy, human kallikrein-related peptidase 2, prostate cancer, prostate-specifi c antigen, tumor markers
in
Clinical Chemistry and Laboratory Medicine
volume
50
issue
11
pages
1993 - 1998
publisher
De Gruyter
external identifiers
  • wos:000310695300019
  • scopus:84872904175
ISSN
1434-6621
DOI
10.1515/cclm-2011-0967
language
English
LU publication?
yes
id
9b11745d-c14c-4482-8dae-8874f9282ac5 (old id 3259298)
date added to LUP
2013-01-07 09:38:35
date last changed
2017-01-01 03:41:33
@article{9b11745d-c14c-4482-8dae-8874f9282ac5,
  abstract     = {Background: The utility of conventional prostate-specifi c antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase 2 (hK2) are eliminated more rapidly after radical prostatectomy. In contrast, all three markers have similarly slow elimination rates after castration induced by gonadotropin-releasing hormone (GnRH) agonists, possibly due to the slow onset of castration. Therefore, we assessed elimination rates of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon (R)), a novel GnRH antagonist. Methods: This study included 24 patients treated with degarelix. Blood was taken at 1, 3, 7, 14, 21 and 28 days after injection of degarelix. Free and total PSA were measured with a commercial dual-label assay, and with inhouse research assays of intact PSA and hK2. Results: Median (interquartile range, IQR) tPSA at baseline was 23.4 (15.8, 59.8). Twenty-two patients (92%) reached castrate levels of testosterone within 24 h of degarelix initiation, and all patients did so within 72 h. All kallikrein forms declined in an exponential fashion after degarelix administration. The median time to 50% reduction in biomarker level was 8-9 days for tPSA or complexed PSA vs. 2-4 days for hK2, iPSA and fPSA. The percentage eliminated at day 3 and day 7 was significantly higher for hK2, iPSA and fPSA than for tPSA (all p&lt;0.02), while tPSA and complexed PSA were similar. Conclusions: The rapid decline of fPSA, iPSA and hK2 after fast induction of castration with degarelix is similar to that reported after prostatectomy and offers a novel, informative method to monitor rapid onset of therapeutic action targeting signaling of the androgen receptor.},
  author       = {Ulmert, David and Vickers, Andrew J. and Scher, Howard I. and Becker, Charlotte and Iversen, Peter and Frankel, David and Jensen, Jens-Kristian and Olesen, Tine Kold and Lilja, Hans},
  issn         = {1434-6621},
  keyword      = {androgen deprivation therapy,human kallikrein-related peptidase 2,prostate cancer,prostate-specifi c antigen,tumor markers},
  language     = {eng},
  number       = {11},
  pages        = {1993--1998},
  publisher    = {De Gruyter},
  series       = {Clinical Chemistry and Laboratory Medicine},
  title        = {Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer: potential for rapid monitoring of treatment responses},
  url          = {http://dx.doi.org/10.1515/cclm-2011-0967},
  volume       = {50},
  year         = {2012},
}