Download a randomized, open label, multicenter, phase iii, 2

Protocols for Advanced Prostate
Cancer and/or Local Failure After
Radical Prostatectomy
Isaac Powell, MD
ARS
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Case Presentation
• Local spread outside of the prostate gland
with or without positive surgical margins
after radical prostatectomy
• Detectable PSA or rising PSA after
surgery
Post-op advanced stage
Prostate Cancer-Specific Survival
Prostate cancer specific
mortality
PSADT
Percent Dead of Prostate Cancer
<2 mo.
<3
<4
<6
<12
D'Amico A, et al. Prostate cancer
mortality based on PSADT after
A RANDOMIZED, OPEN LABEL,
MULTICENTER, PHASE III, 2-ARM STUDY OF
ANDROGEN DEPRIVATION WITH
LEUPROLIDE, +/- DOCETAXEL FOR
CLINICALLY ASYMPTOMATIC PROSTATE
CANCER SUBJECTS WITH A RISING PSA
FOLLOWING DEFINITIVE LOCAL THERAPY
Schematic of Trial Design
RANDOMIZE
• Rising PSA following
radical prostatectomy
• PSA doubling time of <9
months
• Minimum PSA of 1
• Testosterone >100ng/ml
Arm A
•Docetaxel 75 mg/m2 q
3 weeks x 10 cycles
•GnRH agonist x 18
months
•Bicalutamide x 4
weeks
Arm B
•GnRH agonist x 18
months
•Bicalutamide x 4
weeks
The hypothesis of the study is that Progression Free Servival
probability will increase from 50% to 65% a minimum 36
Additional Eligibility
• Subjects in this group may have no
radiographic findings that are clinically
suspicious for metastatic disease.
• Salvage Radiotherapy is allowable and
encouraged where appropriate (for
example, biochemical recurrence with a
positive margin)
Version 3.0 / March 24, 2008 Amendment #2
Primary Objective
• Progression Free Survival within the
period of 18 months of therapy and at
least 18 months follow-up.
• Progression Free Survival is determined
as the time from randomization to:
– the first documentation of detectable PSA or
– radiographic progression or
– to death
Secondary Objectives
• To evaluate cancer specific survival
• To compare overall survival between the 2
treatment groups
• Molecular correlates with clinical outcomes
– Tissue blocks
– Serum/DNA
Radiotherapy Protocol After
Surgery (closed)
Adjuvant Radiotherapy for Pathological
T3N0M0 Prostate Cancer Significantly
Reduces Risk of Metastases and
Improves Survival: Long-Term Followup
of a Randomized Clinical Trial
Ian M. Thompson,*,† Catherine M. Tangen, Jorge Paradelo,
Gary Miller,‡ Dean Troyer, Edward Messing, Jeffrey Forman
Gregory Swanson, Edith Canby-Hagino and E. David Crawfo
Materials and Methods: A total of 431 men
with pT3N0M0 prostate cancer were
randomized to 60 to 64 Gy adjuvant
radiotherapy or observation. The primary
study end point was metastasis-free
survival.
Figure 1
Metastasis-free survival by treatment arm
Conclusions: Adjuvant radiotherapy after
radical prostatectomy for a man with
pT3N0M0 prostate cancer significantly
reduces the risk of metastasis and increases
survival.
Lymph node metastasis
Conclusion
• Locally advanced prostate cancer plus
early aggressive combination therapy
equal long term survival and possibly
“cure”.