Nieuwe Ontwikkelingen in de Behandeling van Kanker prostaatkanker
Testosteron Testosteron geeft zakenvrouwen boost AMSTERDAM - Wil je als zakenvrouw slagen in de financiële wereld dan heb je geluk als je over een hoog testosterongehalte beschikt.
1. LHRH agonist (zoladex, lucrin, eligard) 2. Anti-androgenen
Abiteraterone MDV3100
Cholesterol Cyp11A Pregnenolone Cyp17 Progesterone Cyp17 Cyp17 17α-hydroxypregnenolone Cyp17 17α-hydroxyprogesterone DHEA Cyp17/HSD3β2 Androstenedione 17βHSD CYP17: een belangrijk enzyme Testosterone CYP3A4/3A5 SRD5A2 SRD5A1 CYP1B1 Testosterone breakdown AR DHT AAG
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
Secondary Objectives Response Rates Docetaxel 3 wkly Docetaxel wkly Mitoxantrone Pain Response Rate* n, evaluable 153 154 157 Response rate (%) 35 31 22 P-value (vs. mitoxantrone) 0.01 0.07 PSA Response Rate* n, evaluable 291 282 300 PSA response rate (%) 45 48 32 P-value (vs. mitoxantrone) 0.0005 <0.0001 Tumor Response Rate* n, evaluable 141 134 137 Response rate (%) 12 8 7 P-value (vs. mitoxantrone) 0.1 0.5 * Determined only for patients with pain or PSA 20 or measurable disease at baseline, respectively
Anti-angiogenesis Remming bloedvatvorming
Docetaxel + Thalidomide Overleving P=0.0407 Thalidomide + Docetaxel median 26.9 months Docetaxel Median 14 months Dahut et al J Clin Oncol, 2004
Remming bloedvatvorming Bevacizumab CALBG Phase II study: N=97 estramustine day 1-5 docetaxel day 2 bevacizumab 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
HGF/SF Ras c-met Gab1 Proliferation Sos Grb2 Raf Shp2 ERK/MAPK
100 % van de uitzaaingen hebben c-met (receptor) Control Scatter factor Verspreiding van tumorcellen Bloedvatvorming Studie: Mitoxantrone + AMG102
Immunotherapie (versterking afweer tegen kanker) T-lymfocyte Dendritische cel
Provenge (dendritische cel therapie) Recombinant Prostatic Acid Phosphatase (PAP) antigen combines with resting antigen presenting cell (APC) APC takes up the antigen Antigen is processed and presented on surface of the APC Fully activated, the APC is now sipuleucel- T INFUSE PATIENT Active T- cell Inactive T-cell T-cells proliferate and attack cancer cells Sipuleucel-T activates T-cells in the body The precise mechanism of sipuleucel-t in prostate cancer has not been established.
Sipuleucel-T (Provenge ) Manufacturing Process Day 1 Leukapheresis Day 2-3 Sipuleucel-T is manufactured Day 3-4 Patient is infused Apheresis Center Dendreon Doctor s Office COMPLETE COURSE OF THERAPY: 3 CYCLES
D9901 Fig 2. Primary end point, time to disease progression (intent-totreat population) Small, E. J. et al. J Clin Oncol; 24:3089-3094 2006 Copyright American Society of Clinical Oncology
D9901 Fig 3. Final overall survival (intent-to-treat population) Small, E. J. et al. J Clin Oncol; 24:3089-3094 2006 Copyright American Society of Clinical Oncology
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 cell T - 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 VITAL-1 HRPC w/ mets Chemo-naive asymptomatic N = 600 GVAX Docetaxel + Pred s u r v i v a l VITAL-2 HRPC w/ mets Taxane-naive symptomatic N = 600 Docetaxel + GVAX Docetaxel + Pred s u r v i v a l
GVAX Immunotherapy (CG1940/CG8711) + Ipilimumab (MDX-010: anti-ctla-4) for HRPC
Prostate Cancer Program VUmc 1. rising PSA ET-1A urologie 2. HRPC before chemo G-VAX + MDX retreatment Abiraterone pending 3. HRPC 1 e line NEPRO open 5. HRPC 2nd line AMG102 open 5. HRPC 2nd line RT + MDX pending 6. HRPC 3rd lne MDV3100 pending