©TheCanadian Journal ofUrology™: International Supplement, April 2014
81
Petrylak
compared to<1%ofpatientson themitoxantronearm.
As with neutropenia, diarrhea was more frequently
observed inpatientsover theageof 75. Diarrheaalso
was observed at a 8.6% higher rate in patients who
hadapriorhistoryof radiation therapy. Ahigher rate
of deathdue to adverse eventswas noted inpatients
treated on the cabazitaxel/prednisone arm when
compared to mitoxantrone/prednisone. Of the 18
patients on the cabazitaxel armwho died of adverse
events,7patientsdiedofneutropenicsepsis, incontrast
to1patienton themitoxantronearm. It is tobenoted
that prophylactic colony stimulating factorswerenot
administeredduring the first cycle of therapy, which
could possibly reduce the risk of neutropenic death.
Thispatternof toxicityhas lead theFDAtorecommend
administration of prophylactic growth factors in
patients treatedwith cabazitaxel who are older than
65,havehadextensiveprior radiation,poornutrition,
previous febrileneutropenia,poorperformancestatus
or other serious comorbidities. Ina report of aglobal
earlyaccessprogramperformed inItaly,CRPCpatients
treated with six cycles of cabazitaxel experienced
neutropenia (33.9%), leukopenia (15.6%),anemia (6%),
and asthenia.
29
Table 2 shows common toxicities of
docetaxel and cabazitaxel and theirmanagement.
Two relevant questions regarding sequencing
of cabazitaxel and dosage are being answered by
randomizedclinical trials. Givencabazitaxel’sefficacy
in docetaxel pretreated patients, it would be logical
to evaluate cabazitaxel as front line chemotherapy
inmen with castration resistant prostate cancer. An
international randomized trial of docetaxel combined
with prednisone versus cabazitaxel (20 mg/m
2
or
25 mg/m
2
)/prednisone is underway, clinical trials.
gov NCT01308567. To further define the optional
dose, a second study is randomizingpatients to either
20mg/m
2
or 25mg/m
2
of cabazitaxel, clinical trials.
govNCT01308580.
TABLE 2.
Common toxicitiesofDocetaxel andCabazitaxel and theirmanagement
Drug
Dose/schedule Toxicity
Management
Docetaxel
75mg/m
2
Q3weeks Neutropenia PerASCOguidelines, riskof febrileneutropenia
Contraindications:
<20%, useColonyStimulatingFactors (GCSF,GmCSF)
Baselineneutrophil
basedon age,medical condition, history, disease
count less than 1500 cells/
characteristics.MonitorCBC at leastweekly
µL, ahistoryof severe
hypersensitivity reactions to
docetaxel or polysorbate 80,
severehepaticdysfunction
(bilirubin>Upper limit of
normal (ULN), SGOT
and/or SGPT>1.5XULN
concomitantwith alkaline
phosphatase>2.5XULN
Fluid retention Prophylactic administrationof steroids,monitor
Hypersensitivity withdailyweights, diuretics asneeded
reaction
Corticosteroids, antihistamines,H2antagonists
Neuropathy No standard treatment
Cabazitaxel
25mg/m
2
Q3weeks Neutropenia GCSFprophylaxis recommended for age> 65,
Contraindications:
poor performance status, previous episodes of febrile
Baselineneutrophil count
neutropenia, extensiveprior radiation, poor
less than 1500 cells/µL,
nutritional status, other comorbidities.MonitorCBC
ahistoryof severe
at leastweekly
hypersensitivity
reactions todocetaxel
or polysorbate 80
Diarrhea
Hydration, treatwith antidiarrheals (loperamide).
If ≥grade 3, dosage shouldbemodified
Hypersensitivity Corticosteroids, antihistamines,H2 antagonists
reactions
