Docetaxel with prednisone or prednisolone for the treatment of ...

● Patients with severe fluid retention, such as
pleural effusion, pericardial effusion and
ascites, should be monitored closely.
● No data are available in patients with hepatic
impairment treated by docetaxel in
combination.
● No data are available in patients with severely
impaired renal function.
● The development of severe peripheral
neurotoxicity requires a reduction of dose.
Adverse events
● Severe neutropenia is very common, but is
reversible and not cumulative.
● Non-haematological adverse events occurring in
more than 5% of patients include alopecia, nail
changes, fluid retention, nausea, diarrhoea,
stomatitis/pharyngitis, taste disturbance,
vomiting, sensory neuropathy, anorexia, tearing,
myalgia and fatigue.
Anticipated costs
The cost of docetaxel concentrate for intravenous
infusion is £162.75 for a 0.5-ml vial and £534.75
for a 2-ml vial (both with diluent). 18 Therefore, the
cost of docetaxel at 75 mg/m 2 at 3-weekly intervals
for up to 10 cycles is £11,000. 19
Comparator/alternative
technologies
The US Food and Drug Administration (FDA)
approved the use of mitoxantrone (Novantrone ® ,
Wyeth) plus prednisone as the standard treatment
for mHRPC in the USA in 1996. 20 In the USA,
along with many other Western countries,
mitoxantrone is considered to be one of the most
effective palliative treatments for mHRPC.
Estramustine (Estracyt ® , Pfizer) is an effective
treatment for mHRPC, although it is poorly
tolerated compared with mitoxantrone, especially
by the elderly, and is therefore not widely used. 11
For those patients unable to tolerate
chemotherapy, best supportive care is offered. The
use of corticosteroids is the only form of best
supportive care for which evidence was identified
for this review. The properties of mitoxantrone
and estramustine are described below.
Mitoxantrone
Mitoxantrone is licensed in the UK, but not for
mHRPC, although it is widely used in the UK for
mHRPC patients who are fit for chemotherapy
(Mason M, Professor of Clinical Oncology,
Cardiff University, UK: personal communication,
2005).
© Queen’s Printer and Controller of HMSO 2007. All rights reserved.
Health Technology Assessment 2007; Vol. 11: No. 2
The following section of the report summarises
the product characteristics for mitoxantrone,
(Novantrone ® , Wyeth), available from drug
information online 21 (http://www.drugs.com/pdr/
mitoxantrone_hydrochloride.html).
Mitoxantrone is an anthracenedione, with a
relatively modest toxicity profile apart from
myelosuppression and dose-related cardiotoxicity. 9
It is a DNA-reactive agent that intercalates into
DNA causing crosslinks and strand breaks; it also
interferes with RNA and can inhibit the enzymes
responsible for uncoiling and repairing damaged
DNA.
Mitoxantrone is available as a 20- 25- or 30-mg
concentrate for injection. Mitoxantrone in
combination with corticosteroids is indicated as
initial chemotherapy for the treatment of patients
with pain related to advanced hormone-refractory
prostate cancer (HRPC) in the USA. The
recommended dosage of mitoxantrone is
12–14 mg/m 2 given as a short intravenous infusion
every 21 days. Safety and efficacy in children have
not been established and there are no special
instructions for the use of mitoxantrone in the
elderly; however, the greater sensitivity of some
older individuals has not been ruled out.
Contraindications
● Hypersensitivity to the active substance
● baseline neutrophil count of