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

combination with castration). The anti-androgens bicalutamide and flutamide are approved for use in
combination with LHRH agonists (to offset flare effect and as part of CAB as a longer-term strategy),
with nilutamide also approved for use with bilateral orchidectomy to achieve CAB.
Evidence summary Level References
Castration did not significantly increase cardiovascular mortality
(two trials). However, it did cause a significant decrease in
haemoglobin levels (one trial).
The addition of non-steroidal anti-androgens to castration can result
in an additive increase in toxicities that impair quality of life, such as
hot flushes and gynaecomastia, as well as liver function
abnormalities.
With respect to the most common unwanted effects of androgen
deprivation therapy:
hot flushes are common following all androgen deprivation
therapies, though less so with anti-androgens as
monotherapy,
gynaecomastia and nipple tenderness are a feature of all
ADTs but more so with anti-androgens
liver function and gastrointestinal side-effects: abnormal liver
function tests (LFTs) are a class-effect problem with antiandrogens;
diarrhoea is stated to be a troublesome sideeffect
from flutamide
Cardiovascular morbidity: no increase cardiovascular
mortality was reported in non-oestrogen trials.
other side effects: tiredness and anaemia are commonly
reported.
Recommendation
II 15, 16, 18,
19
II 4, 5, 9,10,
21-34, 35,
36-40
The benefits of androgen deprivation therapy in controlling a patient’s cancer outweigh the
ADT adverse-event profile. However, given the clinically relevant and quality-of-life impairing
litany of unwanted effects of ADT, the timing of commencement of ADT as a palliative
treatment needs to be considered carefully. Assessment of liver function tests, risk of
osteoporosis and bone density measurements as required is recommended. Baseline
information on what is important to each individual patient should be ascertained (refer
chapter 3, p20). This will permit the commencement and nature of treatment to be tailored
and allow an assessment of the cause of adverse effects if they emerge. The common side
effects need to be discussed with the patient before commencing any ADT.
All patients taking anti-androgens should have their liver function tests monitored.
Grade C
5.1.5 Quality of life
Seven randomised controlled trials comparing different hormone therapies and including patients with
metastatic disease examined quality of life outcomes using validated questionnaires. The
questionnaires used were the SWOG QLQ and SF-36 instruments (one trial) and the health-related
Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer
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