©TheCanadian Journal ofUrology™: International Supplement, April 2014
Of note it is likely that chemotherapywill become
even more critical in the management of metastatic
prostate cancer even before the demonstration of
castration resistance. The National Cancer Institute
(NCI) has just announced the preliminary results of
the ECOG 3805 trial (CHAARTED: ChemoHormonal
TherapyVersusAndrogenAblationRandomizedTrial
forExtensiveDiseaseinProstateCancer).
28
Menreceived
eitherADTaloneorADTwith the chemotherapydrug
docetaxel every 3weeks over a period of 18weeks. A
significantimprovementintheoverallsurvivalwasnoted
favoring the participants who had received docetaxel
chemotherapy inaddition to theADT compared to the
ADT alone (3year survival rates of 69.0%versus 52.5%
respectively). Furtheranalysisshowedthatpatientswith
a high extent ofmetastatic disease accounted formost
of thebenefit in theoverall survival fromdocetaxelplus
ADT(3yearsurvivalratesof63.4%versus43.9%forADT
alone). Median followup todate is2years. Fulldetails
are expectedat the 2014ASCOmeeting inChicagobut
this could represent anothermajor paradigm shift and
expanded role for cytotoxic chemotherapy in the initial
therapyofhormonenaïvemetastaticprostatecancer.
Bonehealth inprostate cancer
Bone health is a major issue in prostate cancer as it
can impact qualityanddurationof lifeof thepatients.
The core concepts of “bone health” inprostate cancer
as summarized byDr. Tombal refer to the diagnostic,
primary and pharmacological prevention, and
treatmentofcancertreatmentinducedboneloss(CTIBL)
andmetastasis,andtheirrespectivecomplicationssuch
as osteoporotic fractures and skeletal related events
or SREs.
29
ADT can induce significant changes in
bonemineral density and increase the riskof fracture.
EAU guidelines recommend treating osteoporotic
patients based on DEXA scanning with denosumab
or bisphosphonates, but do not provide guidance
for patients with osteopenia.
30
NCCN guidelines
recommendavarietyofagentssuchasbisphosphonates
(zoledronicacidor alendronate), ordenosumab60mg
SQ every 6months) formenwith ahigh likelihoodof
fractureonandrogendeprivation.
23
Strategies to prevent bone metastasis are also
reviewedherealthough this still remainsamajor issue
to address. The presence of bony metastatic lesions
can further weaken the integrity of the bone. It is
estimated that inmenwithprogressive life threatening
metastatic prostate cancer over 90% ofmenwill have
bonemetastasis. EAUandNCCNtreatmentguidelines
recommendthatbonemetastaticCRPCpatientsshould
receive either zoledronic acidor denosumab andboth
4
Currentmanagement of advanced and castration resistant prostate cancer
223dichloride(formerlyknownasalpharadin) isafirst-
in-class alpha particle-emitting radiopharmaceutical
approved for the treatment of patients with CRPC
with symptomatic bone metastases and no known
visceral metastasis. Radium 223, a calciummimetic,
targetsbonebutasanalphaemitterhasashorterrange
with lessbonemarrow toxicitywhencompared to the
existingbeta emitting agents.
Radium 223 dichloride has been included in the
latest 2014 edition of the National Comprehensive
Cancer Network (NCCN) prostate cancer treatment
guidelines where it has been given a category 1
recommendation as both a first-line and second-line
option for the treatment of patientswith symptomatic
bonemetastasesandnoknownvisceraldisease.
23
The
roleofall radiopharmaceuticals including thepractical
considerations in theuseof radium223 isdiscussedby
Dr.Denandassociates.
24
Chemotherapy formCRPC
Historically, no chemotherapeutic agents had been
shown tobeeffective in themanagementofadvanced
prostatecancer. Theonlyagent formallyapproved for
metastatic prostate cancer progressing on hormonal
ablation before 2004 was mitoxantrone and that
indication was only for palliation when used in
combinationwithprednisone. In2004docetaxelwas
formally approved “with prednisone in androgen
independent (hormonerefractory)metastaticprostate
cancer”.
25,26
This taxane served as the mainstay for
prostate cancer that escaped hormone suppression
until thenextmedication sipuleucel-Twas approved
in 2010. Docetaxel has remained as an important
agent in this patient population and many of the
newer drugs approved including abiraterone and
enzalutamidewere initially approved only after this
chemotherapyhad failed. Cabazitaxel, amicrotubule
inhibitor related to docetaxel, has also recently been
approved in the post-docetaxel setting. The official
labelstatescabazitaxel is indicated incombinationwith
prednisone for treatment of patients with hormone-
refractorymetastaticprostatecancerpreviously treated
with a docetaxel-containing treatment regimen.
27
Whilemuch excitement has beengenerated amongst
allof theneweragentsrecentlyapproved formCRPC,
chemotherapy remainsaprovenoption. Dr.Petrylak,
an early pioneer in the use of docetaxel in prostate
cancer, provides a review on the recent history of
chemotherapy for prostate cancer and explains the
effectivemanagementstrategies tomaximizeoutcome
and limit toxicity using docetaxel and cabazitaxel
chemotherapy formCRPC.
26
