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Prostaatkanker: Behandeling door oncoloog
Jarmo Hunting11-04-2013
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Prostaatkanker | Jarmo Hunting | 7 april 20131
Inhoud presentatie
Inleiding
Anti-hormonale therapie
Chemotherapie
Targeted therapy (TKI)
Supportive care
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Prostaatkanker | Jarmo Hunting | 7 april 20132
Inleiding
Gemetastaseerd prostaatcarcinoom-genezing niet mogelijk;-doel is behouden/verbeteren kwaliteit van leven,-alsmede verbeteren levensverwachting.
Patienten verwezen door uroloog: castratie resistent-LHRH agonist niet (meer) werkzaam-Testosteron op castratieniveau-Anti-androgeen niet (meer) werkzaam (MAB)
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PSA progressie is geen behandelindicatie in CRPC
Vier sleutelfactoren bepalen overleving:-Bloedarmoede-2 of meer nieuwe botmetastasen op botscan-Metastasen in vitale organen (long, lever, …)-Pijnklachten
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Prednison
Wordt na LHRH-a en MAB toegevoegd aan behandeling.
Onderdrukt ACTH en daarmee androgeenproductie bijnier
Verbetert kwaliteit van leven, vermindert pijn en moeheid
Vermindert bijwerkingen chemotherapie
Tannock, JCO 1989; Dorf and Crwaford, Ann Oncol 2012; Fossa, JCO 2001
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Chemotherapie
Huidige generatie chemotherapie:-Docetaxel/prednison (Taxotere)-Cabazitaxel/prednison (Jevtana)
Voorwaarden:-Fit-Goede nierfunctie/leverfunctie-Meer dan PSA progressie
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Docetaxel (Taxotere)
Intraveneuze chemotherapieIn combinatie met prednisonToediening 1x/3 weken op dagbehandeling- 10 kurenGeeft overlevingswinst
Bijwerkingen: onderdrukking beenmerg, haarverlies, maag-darmbezwaren, allergische reactie
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Prostaatkanker | Jarmo Hunting | 7 april 20138
Cabazitaxel (Jevtana)
Intraveneuze chemotherapieNa eerdere behandeling met docetaxelIn combinatie met prednisonToediening 1x/3 weken op dagbehandeling- 10 kurenGeeft overlevingswinst
Bijwerkingen: onderdrukking beenmerg, haarverlies, maag-darmbezwaren, allergische reactie
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Prostaatkanker | Jarmo Hunting | 7 april 20139
Anti-hormonale therapie
Klassieke middelen:-LHRH agonist/antagonist; castratie-Anti-androgenen
CYP17-remmers:-Abiraterone/prednison (Zytiga)-(Orteronel/prednison)
Nieuwe generatie AA: -(Enzalutamide/prednison) (Xtandi)
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Abiraterone (Zytiga)
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Abiraterone (Zytiga)
Remt androgeen productieGeregistreerd NA en VOOR chemotherapie behandelingOnderhoudsbehandeling tabletten: 1000 mg/dIn combinatie met prednisonGeeft overlevingswinst
Bijwerkingen: problemen in water-zouthuishouding, hoge bloeddruk, leverprikkeling
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Enzalutamide (Xtandi)
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Enzalutamide (Xtandi)
Sterke binding aan androgeen receptorIn USA geregistreerd, in EU/NL ws. najaar 2013Vergoeding ws. voorjaar 2014Onderhoudsbehandeling tabletten, 160 mg/dIn combinatie met prednisonGeeft overlevingswinst
Bijwerkingen: moeheid, spierpijn, hoofdpijn, opvliegers, hoge bloeddruk
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Conclusies
Eerste lijns therapie: docetaxel
Indien fit: tweede lijns therapie: cabazitaxel
Abiraterone of Enzalutamide: derde lijns therapie
Abiraterone EN Enzalutamide geeft ws. weinig winst
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Ondersteunende therapie
•Strontium, Samarium, Rhenium•(Alpharadin)
•Zolendroninezuur (Zometa)•Denosumab (Xgeva)
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Samarium, Strontium, Rhenium
Radioactieve stoffenIntaveneuze toediening op nucleaire afdelingDoel is pijnbestrijding bij pijnlijke botmetastasen (75%)Rhenium en samarium sneller effect, strontium langdurigerBehandeling kan herhaald wordenGeen overlevingswinst
Bijwerking: onderdrukking beenmerg
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Alpharadin
Radium-223: radioactieve stof, gedraagt zich als calciumMaandelijkse toediening (6x)Niet beschikbaar in NederlandGeeft overlevingswinst en minder SRE
Bijwerkingen: onderdrukking beenmerg, diarree, botpijn
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Zolendroninezuur (Zometa) Denosumab (XGEVA)
Bisfosfonaat, RANKL-MabRemming osteoclastenIntraveneus 1 x/mnd, Subcutaan 1x/mnd
Effectief op Skeletal Related Events (SRE):-Botpijn waarvoor bestraling noodzakelijk is-(Tijd tot optreden) fracturen-Noodzaak tot operatie-Neurologische complicaties (mn ruggenmerg)Geen overlevingswinst
Bijwerkingen: kaaknecrose, laag calcium
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TKI: Cabozantinib
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TKI: Cabozantinib
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TKI: Cabozantinib
Fase 3 studie DUOS (St Antonius Ziekenhuis): COMET-1
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Studies met overlevingswinst in mCRPC: 7
NR vs 27.20.75Abiraterone/prednison vsplacebo/prednison
mCRPC, weinigsymptomen
COU-AA-302N =
18.4 vs 13.60.63Enzalutamide vs prednisonNa docetaxelAFFIRMN = 1199
14.9 vs 11.30.70Radium-223/BSC vsplacebo/BSC
Voor/Nadocetaxel
ALSYMPCAN = 921
14.8 vs 10.90.65Abiraterone/prednison vsplacebo/prednison
Na docetaxelCOU-AA-301N = 1195
15.1 vs 12.70.70Cabazitaxel/prednison vsmitoxantrone/prednison
Na docetaxelTROPICN = 755
25.8 vs 21.70.78Sipuleucel-T vs controlemCRPC, weinigsymptomen
IMPACTN = 512
18.9 vs 16.50.76Docetaxel/prednison vsmitoxantrone/prednison
mCRPCTax 327N = 1006
Overleving(mnd)
HROntwerpStatus mPCStudie
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Docetaxel
TAX 327 studie (JCO 2008):
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Docetaxel
TAX 327 studie (JCO 2008):
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Cabazitaxel
TROPIC study (Lancet 2010):
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Cabazitaxel
TROPIC study (Lancet 2010):
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Abiraterone acetaat NA chemotherapie
COU-AA-301 studie (NEJM 2010):
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Abiraterone acetaat NA chemotherapie
COU-AA-301 studie (NEJM 2010):
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Abiraterone acetaat VOOR chemotherapie
COU-AA-302 studie (NEJM 2013):
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Abiraterone acetaat VOOR chemotherapie
COU-AA-302 studie (NEJM 2013):
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Enzalutamide (AFFIRM)
NEJM 2012, Scher, 367 (13): 1187
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TKI: Cabozantinib
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TKI: Cabozantinib
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TKI: Cabozantinib
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Alpharadin
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Alpharadin