Universität zu Köln

Mikah, Phillip, Krabbe, Laura-Maria, Eminaga, Okyaz, Herrmann, Edwin, Papavassilis, Philipp, Hinkelammert, Reemt, Semjonow, Axel, Schrader, Andres-Jan and Boegemann, Martin (2016). Dynamic changes of alkaline phosphatase are strongly associated with PSA-decline and predict best clinical benefit earlier than PSA-changes under therapy with abiraterone acetate in bone metastatic castration resistant prostate cancer. BMC Cancer, 16. LONDON: BMC. ISSN 1471-2407

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Abstract

Background: Significant progress in treatment of metastatic castration resistant prostate cancer (mCRPC) has been made. Biomarkers to tailor therapy are scarce. To facilitate decision-making we evaluated dynamic changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and prostate specific antigen (PSA) under therapy with Abiraterone. Methods: Men with bone mCRPC (bmCRPC) on Abiraterone 12/2009-01/2014 were analyzed. Dynamic ALP-, LDH- and PSA-changes were analyzed as predictors of best clinical benefit and overall survival (OS) with logistic-regression, Cox-regression and Kaplan-Meier-analysis. Results: Thirty-nine pre-and 45 post-chemotherapy patients with a median follow up of 14.0 months were analyzed. ALP-Bouncing can be observed very early during therapy with Abiraterone. ALP-Bouncing is defined as rapidly rising ALP-levels independent of baseline ALP during the first 2-4 weeks of Abiraterone-therapy with subsequent equally marked decline to pretreatment levels or better within 8 weeks of therapy, preceding potentially delayed PSA-decline. In univariate analysis failure of PSA-reduction >= 50 % and failure of ALP-Bouncing were the strongest predictors of progressive disease (p = 0.003 and 0.021). Rising ALP at 12 weeks, no PSA-reduction >= 50 % and no ALP-Bouncing were strongest predictors of poor OS, (all p < 0.001). Kaplan-Meier-analysis showed worse OS for rising ALP at 12 weeks, no PSA-reduction >= 50 % and no ALP-Bouncing (p < 0.001). In subgroup-analysis of oligosymptomatic patients all parameters remained significant predictors of poor OS, with no PSA-reduction >= 50 % and rising ALP at 12 weeks being the strongest (p < 0.001). In multivariate analysis PSA-reduction >= 50 % remained an independent predictor of OS for the whole cohort and for the oligosymptomatic subgroup (both p = 0.014). No patient with ALP-Bouncing had PD for best clinical benefit. Patients with rising ALP at 12 weeks had no further benefit of Abiraterone. Conclusions: Dynamic changes of ALP, LDH and PSA during Abiraterone-therapy are associated with best clinical benefit and OS in bmCRPC. ALP-Bouncing occurring earlier than PSA-changes as well as prior to equivocal imaging results and rising ALP at 12 weeks under Abiraterone may help to decide whether to discontinue Abiraterone. An external validation of these findings on a prospective cohort is planned.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mikah, Phillip UNSPECIFIED UNSPECIFIED UNSPECIFIED Krabbe, Laura-Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Eminaga, Okyaz UNSPECIFIED UNSPECIFIED UNSPECIFIED Herrmann, Edwin UNSPECIFIED UNSPECIFIED UNSPECIFIED Papavassilis, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Hinkelammert, Reemt UNSPECIFIED UNSPECIFIED UNSPECIFIED Semjonow, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Schrader, Andres-Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Boegemann, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-281483
DOI:	10.1186/s12885-016-2260-y
Journal or Publication Title:	BMC Cancer
Volume:	16
Date:	2016
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1471-2407
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INCREASED SURVIVAL; END-POINTS; PHASE-II; MITOXANTRONE; DOCETAXEL; PREDNISONE; ENZALUTAMIDE; RADIUM-223; TRIALS Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28148