Clinical Practice Guidelines for the management of locally advanced ...

the median overall survival for patients with castrate-resistant prostate cancer is now 18 months from
the start of chemotherapy. 14 It is of note that the median overall survival is detailed to be about 12
months from institution of second-line hormone manipulation in the studies listed. These studies were
done prior to the demonstrated benefit of docetaxel for patients with castrate-resistant prostate cancer.
Specifically, prior studies have shown mitoxantrone plus prednisone was associated with a better
palliative response than the prednisone (low-dose corticosteroid) alone. It is also of note that in the
pivotal docetaxel plus prednisone versus mitoxantrone plus prednisone studies 14 , patients had a
median of four previous hormone manipulations, indicating common use of hormone manipulations
prior to trialling chemotherapy. It is of relevance to point out the ‘clock’ for the median overall
survival of about 18.5 months for docetaxel and 16.4 months for mitoxantrone started from when the
chemotherapy was given (ie after the hormone manipulations). It is also worth noting that more
recently, agents which (i) block the formation of testosterone from cholesterol by inhibiting an
enzyme known as 17-hydroxylase/17,20 lyase (abiraterone), and (ii) are more potent antagonists of
the androgen receptor, have been shown to cause disease regression as single agents in the postchemotherapy
setting. These agents are being assessed in patients with castrate-resistant disease (for
example the NCT00638690 or COU-AA-301 trial of abiraterone acetate). These are well-powered
studies and will provide important information about the utility of second-line hormone manipulations
in patients with castrate disease.
Evidence summary Level References
Data from large randomised studies are limited.
No second-line hormone manipulation in an RCT has been clearly
shown to lead to an improvement in overall survival.
A minority of patients have prolonged disease control with further
hormone manipulations such as an anti-androgen or adrenal
androgen suppression with ketoconazole and hydrocortisone
In one RCT, overall quality of life scores, pain scores and
gastrointestinal symptom scores were significantly better with
prednisone compared with flutamide.
II 2-11, 15-17
When assessing the data in total and in the context of the role of docetaxel (active chemotherapy), a
recommendation of a course of action can be made for patients with evidence of progression on
androgen deprivation.
Recommendation
There is a sequence of actions that should be followed when a patient is shown to have
progressive cancer on androgen deprivation therapy. First, confirm that the patient has a
castrate level of testosterone if on an LHRH agonist therapy. If the patient is also on a nonsteroidal
anti-androgen, this agent could be withdrawn and observed for the possibility of an
anti-androgen withdrawal phenomenon. It is reasonable to trial further hormone
manipulations if the patient is asymptomatic or minimally symptomatic prior to use of
chemotherapy (e.g. docetaxel).
Grade C
Bisphosphonates, radiotherapy and chemotherapy will need to be integrated at some time into overall
treatment regimens at this stage of the disease.
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Castration-resistant prostate cancer