©TheCanadian Journal ofUrology™: International Supplement, April 2014
AddresscorrespondencetoDr.DanielP.Petrylak,Department
of Urology andMedical Oncology, Yale University Cancer
Center,789HowardAve,FMP312,NewHaven,CT06519USA
Practical guide to theuseof chemotherapy in
castration resistant prostate cancer
Daniel P. Petrylak,MD
Department ofMedicine (MedicalOncology) andUrology, YaleCancerCenter,NewHaven, Connecticut,USA
PETRYLAK DP. Practical guide to the use of
chemotherapy incastrationresistantprostatecancer.
Can JUrol
2014;21(Suppl 1):77-83.
Introduction:
Chemotherapy,oncethoughttobetoxicand
ineffective inmenwithcastrationresistantprostatecancer
(CRPC), hasasignificant impactonsurvival andquality-
of-life in these patients. This article summarizes recent
studiesperformedwithtwoFoodandDrugAdministration
(FDA) approved agentswhichhave improved survival in
menwithCRPC, docetaxel and cabazitaxel.
Materials and methods:
The literature on cytotoxic
chemotherapy for castration resistant prostate cancer
was reviewed. The individual efficacy, mechanisms of
chemotherapeutic action, and appropriate disease states
of administration were identified. Recent clinical trial
results of chemotherapy combined with targeted agents
was also reviewed.
Results:
Front linecytotoxictherapyconsistsofdocetaxel
combined with prednisone. In two randomized trials,
docetaxel based therapy demonstrated a 20%-24%
improvement in survival over the palliative standard
of care, mitoxantrone combinedwith prednisone. Eight
randomized trials combining docetaxel/prednisone with
otherantiangiogenic, bone targeted, vaccineormetabolic
therapies failed to demonstrate an improvement in
survival over docetaxel alone. Cabazitaxel, an analogue
of docetaxel which has activity in taxane resistant cell
lines, is approved by the FDA, for use inCRPCpatients
who have previous exposure to docetaxel.
Conclusions:
Docetaxel combined with prednisone
remains the standard of care as first line cytotoxic
therapy for CRPC. Cabazitaxel is an effective second
line cytotoxic agent that improves survival; studies are
underwaycomparingcabazitaxel todocetaxel asfirst line
chemotherapy. Given its lack of survival benefit, aswell
as the emergence of new treatments for prostate cancer,
mitoxantrone has a diminished role in the treatment of
CRPC.
Key Words:
castration resistant prostate cancer,
docetaxel, cabazitaxel, chemotherapy
from boney metastases, improvement in neurologic
symptomsfromspinalcordcompression,andadecline
inserumprostate-specificantigen(PSA). Despite initial
clinicalandsymptomatic improvement,nearlyallmen
will progress to castration resistant prostate cancer
(CRPC). Thisstateofdisease isdefinedasprogression
of faceofcastrate testosterone levels,historicallyhave
adismalprognosiswithmediansurvival timesof9-12
months. In addition, the morbidity associatedwith
CRPC is significant as metastases to bone can lead
to spinal cord compression, fractures, pain, cachexia,
anemia, andultimatelydeath.
In the 1990s, themanagement ofCRPCwas limited
to palliation of symptoms, due to a lack of effective
Introduction
It is estimated that more than 29000 men will die
frommetastatic prostate cancer in 2014, making it
the second leading cause ofmale cancer death.
1
The
initial treatment for metastatic disease is surgical or
medical castration; reduction in testosterone to levels
of less than 50 ng/dL can rapidly and dramatically
result inprostate tumorregression.
2
Clinical response
toandrogenblockade ismanifestedbya relief inpain
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