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Prostate Cancer: What’s New? Treatment Options For Advanced Castrate Resistant Disease. Naomi B Haas, MD Associate Professor of Medicine Abramson Cancer Center. April 24, 2013. Objectives: to discuss the new modulation of androgen and the androgen receptor for prostate cancer.
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Naomi B Haas, MD
Associate Professor of Medicine
Abramson Cancer Center
April 24, 2013
Pills Implants and shots
LHRH antagonist- degarelix
Scholz M et al. J Urol. 2005 Jun;173(6):1947-52.
0 1 to 3, >3 lesions bone scan
25, 35, and 18 patients
Median and mean time to PSA progression was 6.7 and 14.5 months.
Median and mean survival time was 38.0 and 42.4 months, respectively.
Response time and survival were highly correlated (r = 0.799). A total of 34 (44%) men had a greater than 75% decrease in PSA. The median survival times in men with more vs less than a 75% decrease were 60 vs 24 months, respectively.
Lyase inhibitors- get rid of intratumoral testosterone and residual sources of testosterone/androgens
AR inhibitors- address mutations in the receptor, splice variants
Other AR Modulators
HSP 90 inhibitors
Abiraterone acetate and prednisone in patients (Pts) with progressive metastatic castration resistant prostate cancer (CRPC) after failure of docetaxel-based chemotherapy.JClinOncol 26: 2008 (May 20 suppl; abstr 5019)
AA (Zytiga) 1000mg qd + pred 5mg twice daily
14 of 35 pts had decrease in PSA of >50%
Phase III trial completed post chemotherapy showed overall survival improvement of almost 5 months in a study of 1000+ patients, leading to FDA approval
or are not suitable
Failed 1 or 2 prior
Improvement in overall survival of more than 5 months
Closed to accrual in the US
Optional FDHT-PET at Baseline, 4 and 12 wks
Q 12 wks
PSA and CTC
Q 4 wks
ARN-509 once daily until progression
PK week Continuous Daily Dosing
Wk 1 2 3 4 5 9 13
Cycle 1 2 3
DLT period for dose escalation
OF AR INHIBITION IN RESPONSE TO ARN-509
ASCO GU 2013
Hormone Sensitive v. Hormone Refractory Prostate Cancer
Open or Planned at
1. High risk RT+ ADT+/- docetaxel trial
2. everolimus + salvage XRT
3. Phase I Docetaxel/ cmet inhibitor trial
4. CAR-T cells in advanced disease
5. TKI258 plus INC280