Die prognostische Relevanz eines initialen PSA-Anstiegs unterChemotherapie mit Docetaxel bei hormonrefraktäremProstatakarzinom
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Philipps-Universität Marburg
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Abstract
The hormone refractory stage of prostate cancer developes 18-36
months after medicinal or surgical treatment. An asymptomatic progress
marked by PSA surges is appearing earlier than the disease
progression with bone pain and anaemia. Until today, the treatment of
HRPC, independent of the beginning, represents just a palliative option.
At the moment the available treatment can only prolong the progress
free period.
Recently, two independent phase-III-studies provided evidence that
docetaxel based chemotherapy significantly prolongs survival among
men with hormone-refractory prostate cancer. Therefore, in 2004
docetaxel was approved for treatment of HRPC and is now the standard
first-line therapy in many urological departments. The determination of
the Serum PSA is regarded as a suitable tool for response evaluation
during both local and systemic treatment of prostate cancer. In most
cases the PSA level correlates with the tumour volume, and a 30%
decrease or more of PSA during chemotherapy of HRPC has been
associated with prolonged survival. Initial PSA surges are well known in
androgen-deprivation therapy of advanced prostate cancer. This so
called flare phenomenon has also been observed in HRPC patients
treated with liposomal doxorubicin. Initial PSA increases in the range of
37-514% during the first 4-8 weeks could be observed. So far no study
evaluated the clinical significance and prognostic relevance of these
initial PSA surges in patients receiving doxorubicin.
Until today we have also observed this flare phenomenon in a
significant fraction of patients receiving docetaxel for treatment of
HRPC. In this study the incidence and clinical impact of a flare
phenomenon was evaluated, particularly with regard to the question if
these reversible PSA increases might predict unfavourable prognosis
Zusammenfassung
50
and should lead to an early discontinuation or change of treatment.
Since 2002, 41 patients with HRPC were treated with a docetaxel
based first-line regime at the university hospital in Marburg.
A PSA flare phenomenon after 7 weeks could be identified for 5
patients (12,2%). A continuous PSA decline could be observed for 24
(58,5%) patients, complete therapeutic failure was recognized for 12
(29,2%) patients marked by an irreversible PSA surge. Kaplan-Meier-
Survival analysis revealed that the mean survival for patients with a
PSA flare phenomenon (group 3) was not different from primary
responders (group 1) (p=0,434). In contrast, the mean survival of those
patients who completely failed to respond to docetaxel (group 2) was
noticeably shorter, so that the mean survival time of those patients
(group 2, Progression) is statistically totally different to the mean
survival of group 1 (Response) and group 3 (Flare) (p= 0,001 and
0,007).
The pathophysiologic basis for the flare phenomenon remains elusive.
One explanation might be that HRPC represents a malignant condition
with immense intercellular heterogeneity concerning drug sensitivity,
cell cycle kinetics and PSA expression. A different explanation could be
the release of PSA from lytic tumour cells and thus might reflect a
certain sensitivity of the tumour cells to the chemotherapy. The present
study clearly indicates that patients showing an initial PSA flare
phenomenon and patients with immediate biochemical response have
about the same prognosis. Therefore, an initial rise of PSA should not
result in early discontinuation of docetaxel based treatment; at least if
there are no signs of disease progression.
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Dates
Created: 2008Issued: 2008-05-23Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
PSA flare phenomenonHormone refractory prostate cancerDocetaxel
DFG-subjects
PSA-Flare-upHormonfefraktäres ProstatakarzinomsDocetaxel
DDC-Numbers
610
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Kräuter, Petra Monica: Die prognostische Relevanz eines initialen PSA-Anstiegs unterChemotherapie mit Docetaxel bei hormonrefraktäremProstatakarzinom. : Philipps-Universität Marburg 2008-05-23. DOI: https://doi.org/10.17192/z2008.0355.
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This item has been published with the following license: In Copyright