If you can't read please download the document
Upload
phungdung
View
225
Download
1
Embed Size (px)
Citation preview
Nieuwe Ontwikkelingen
in de
Behandeling van Kanker
prostaatkanker
Testosteron
Testosteron geeft zakenvrouwen boostAMSTERDAM - Wil je als zakenvrouw slagen in de financile
wereld dan heb je geluk als je over een hoog testosterongehalte beschikt.
1. LHRH agonist (zoladex, lucrin, eligard)
2. Anti-androgenen
Abiteraterone
MDV3100
CholesterolCyp11A
PregnenoloneCyp17
Progesterone
Cyp17
17-hydroxyprogesterone
Cyp17/HSD32
Androstenedione
17HSD
Testosterone
CYP3A4/3A5
CYP1B1
Testosteronebreakdown
SRD5A2SRD5A1
DHT
AR AAG
17-hydroxypregnenolone
Cyp17
Cyp17
DHEA
CYP17: een belangrijk enzyme
Abiteraterone (na chemotherapie)
16/34 (47%) pts 50% PSA daling
22/34 (65%) pts 30% PSA daling
MDV3100: Androgeen Receptor Antagonist (small molecule)
Hormonale therapie
voor start chemotherapie
na chemotherapie
nieuwe studies
Nieuwe Ontwikkelingen
in de
Behandeling van Kanker
chemotherapie
Wanneer te starten met chemotherapie ?
Botuitzaaingen: pijn destructie dwarslesie beenmerg suppressie
Uitzaaingen in lymfklieren: obstructie nierfunctie verlies
Docetaxel3 wkly
Docetaxel wkly Mitoxantrone
Pain Response Rate*n, evaluable 153 154 157Response rate (%) 35 31 22P-value (vs. mitoxantrone) 0.01 0.07
PSA Response Rate*n, evaluable 291 282 300PSA response rate (%) 45 48 32P-value (vs. mitoxantrone) 0.0005
Anti-angiogenesisRemming bloedvatvorming
Docetaxel + Thalidomide Overleving
Dahut et al J Clin Oncol, 2004
Thalidomide + Docetaxelmedian 26.9 months
DocetaxelMedian 14 months
P=0.0407
Remming bloedvatvorming
Bevacizumab
CALBG Phase II study: N=97
estramustine day 1-5docetaxel day 2bevacizumab day 2
PSA response 81%
Median survival 21 months
Anti -angiogenesis
Docataxel + Thalidomide II (N=60) 90% PSA 63% Response+ Bevacizumab
Docetaxel + sunitinib (Sutent) II (N=44) 50% PSA 39% Response
Chemotherapie
start niet te laat
combinatie met remmers
van bloedvatvorming hoopvol
nieuwe studies
Verspreiding van
tumorcellen
ERK/MAPK
HGF/SF
Ras
Raf Shp2
Gab1
Proliferation
c-Met
SosGrb2
Control Scatter factor
100 % van de uitzaaingen hebben c-MET (receptor)
Bloedvatvorming
Verspreiding van tumorcellen
Studie: Mitoxantrone + AMG102
Immunotherapie(versterking afweer tegen kanker)
T-lymfocyte Dendritische cel
Provenge (dendritische cel therapie)
APC takes up the antigen
Recombinant Prostatic Acid Phosphatase (PAP)
antigen combines with resting antigen presenting
cell (APC)
Fully activated, the APC is now sipuleucel-
T
The precise mechanism of sipuleucel-T in prostate cancer has not been established.
Antigen is processed and presented on
surface of the APC
INFUSE PATIENT
T-cells proliferate and attack
cancer cells
Sipuleucel-T activates T-cells in
the body
Active T-cell
Inactive T-cell
Sipuleucel-T (Provenge)Manufacturing Process
COMPLETE COURSE OF THERAPY:3 CYCLES
Day 1Leukapheresis
Day 2-3Sipuleucel-T is manufactured
Day 3-4Patient is infused
Apheresis Center Dendreon Doctors Office
Copyright Am erican Society o f Clinical Oncology
Small, E. J. et al. J Clin Oncol; 24:3089-3094 2006
D9901Fig 2. Primary end point, time to disease progression (intent-to-
treat population)
Copyright Am erican Society o f Clinical Oncology
Small, E. J. et al. J Clin Oncol; 24:3089-3094 2006
D9901Fig 3. Final overall survival (intent-to-treat population)
Ipilimumab (MDX-010)
anti-human CTLA-4 Antibody
fully human IgG1k antibody
blocks the binding of CTLA-4 to B7
does not mediate ADCC
Ipilimumab (MDX-010)
Radiotherapy of bone lesions + Ipilimumab
Radiotherapy bone lesions + Ipilimumab
Prostate cancer (immunotherapy)
Irradiated, autologous tumor cells transduced with the GM-CSF gene
Dendritic cellT - cell
Anti-tumor Activity
GVAX Phase 2 Studies in HRPC
Pijn ter plaatse van injecties Jeuk, zwelling
Overleving: bemoedigend 2.5 jaar
Prostate GVAX Phase 3 Program
survival
Docetaxel + Pred
GVAXVITAL-1
HRPC w/ metsChemo-naiveasymptomatic
N = 600survival
Docetaxel + Pred
Docetaxel + GVAXVITAL-2
HRPC w/ metsTaxane-naivesymptomatic
N = 600
GVAX Immunotherapy (CG1940/CG8711) + Ipilimumab (MDX-010: anti-CTLA-4) for HRPC
Prostate Cancer Program VUmc1. rising PSA ET-1A urologie
2. HRPC before chemo G-VAX + MDX retreatmentAbiraterone pending
3. HRPC 1e line NEPRO open
5. HRPC 2nd line AMG102 open
5. HRPC 2nd line RT + MDX pending
6. HRPC 3rd lne MDV3100 pending