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Chemohormonal Therapy: New
Paradigm in the Treatment of
Metastatic Prostate Cancer —
Why, When, and How?
馮思中 教授
長庚紀念醫院泌尿腫瘤科
Targeting prostate cancer cell with different mechanisms of action
攝護腺癌病人的自然病史
標準去勢治療
局部治療
Denosumab、Zoledronic Acid
鐳-223
[TITLE]
病情進展/PSA值
Enzalutamide
開始荷爾蒙治療
去勢治療
Abiraterone 澤珂錠
抗雄性素後續治療
化療
死亡
開刀／放射
化療後
化療?
化療?
Sipuleucel-T
歐洲紫杉醇
時間
Presented By William K. Oh, MD at 2013 ASCO Annual Meeting
第二代歐洲紫杉醇
Phase III clinical trials in mCRPC treatment
COU-AA-302
Median overall survival was significantly longer in the abiraterone acetate
group than in the placebo group (34·7 months [95% CI 32·7–36·8] vs
30·3 months [28·7–33·3]; hazard ratio 0·81 [95% CI 0·70–0·93];
p=0·0033).
Lancet Oncology Volume 16, No. 2, p152–160, February 2015
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In addition to improving overall survival relative to placebo,
enzalutamide significantly improves patient-related outcomes and
delays occurrence of first skeletal-related event in chemotherapynaive men with metastatic castration-resistant prostate cancer.
What is the best treatment sequence for CRPC?
OS range from 7.1 to 15.8m
Phase III trial needed to find out what is the best sequence of treatment.
Early use of chemotherapy in prostate cancer: is this rationale?
Why chemo-hormonal work better?
1. The use of early chemotherapy may address the phenotypically
heterogeneous subpopulation of tumor cells and eliminate
androgen-independent clones, allowing for a potentially
improved therapeutic effect.
2. The early use of cytotoxic chemotherapy may improve
outcomes by attacking clones resistant to ADT before they
expand or acquire more resistance or simply killing more cancer
cells when they are more vulnerable
3. Therapy works best when it is multitargeted, administered in a
lesser disease volume as a preemptive strike before adaptive
resistance. Other potential factors include better drug tolerance
and less toxicity in less sick patients.
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK e263
high-volume disease: visceral metastasis and/or four or more bone metastases with at least
one beyond axial skeleton (pelvis and vertebral column).
Comparison of AFU 15 and E3805 trial
Concerns regarding AFU 15 trial:
1. Relatively small sample size
2. Substantial percentage of patients with good prognostic factors at baseline: 49%
in the ADT plus docetaxel group and 50% in ADT alone.
3. High toxicity reported, > 10% incidence of grade 3 neutropenia and four deaths in
ADT plus docetaxel; 21% discontinued in docetaxel plus ADT group
4. Cross-over treatments: 62% of patients given ADT alone received
docetaxel at progression, compared with 28% of patients given ADT plus docetaxel
who were re-treated with docetaxel.
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK e263
Systemic Therapy in Advancing or Metastatic Prostate Cancer:
Evaluation of Drug Efficacy (STAMPEDE)
Median survival was increased by 10m
from 67m on SOC to 77m on SOC+D
Adjuvant chemotherapy improves overall survival in
high-risk, localized prostate cancer—ASCO 2015
Results:
The 4-year OS rates were 89%
for men who received ADT and
RT versus 93% for men treated
with ADT, RT, and docetaxel
(HR = 0.70; 90% CI, 0.510.98; P = 0.04).
5-year disease-free survival
rates were 66% in the
standard therapy group versus
73% in the docetaxel group
(HR = 0.76; 95% CI: 0.571.00; P = .05)
Prostate cancer is five different diseases,
experts say
Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery
and validation cohort study. EBioMedicine, 2015; DOI: 10.1016/j.ebiom.2015.07.017
Conclusion



Many drugs are currently available for CRPC
therapy.
New evidences suggested that early
chemotherapy may be beneficial for certain
hormone naïve metastasis prostate cancer
(mPca).
The best treatment algorithm for mPCa has yet
to be determined.
Thank you