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

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Appendix 6
Study details and Participant details Intervention details Results Conclusion and
design comments
Outcome 4: PSA decline
PSA decline of ≥ 50% (N = 612)
I: 155/309 (50%)
C: 82/303 (27%)
(p < 0.001)
Outcome 5: Adverse events
Adverse events (measured using the NCI CTC, version 2;
grade 3 (severe)/4 (life-threatening)/5 (fatal) (N = 658):
I (n = 330) C (n = 328)
Control:
12 mg mitoxantrone
per m 2 body surface area
i.v. on day 1, + 5 mg
prednisone 2 × daily. Given
in 21-day cycles.
Dose of mitoxantrone
increased to 14 mg/m 2 if
no grade 3–4 adverse
events during first cycle.
Treatment continued until
disease progression or
unacceptable adverse
events, or until 144 mg/m 2
mitoxantrone administered
Age range of participants:
I, 47–88 years; C, 43–87 years
Other participant characteristics:
Race:
White: I, 86%; C = 82%
Black: I = 12%; C = 15%
Hispanic: I = 7%; C = 6%
Asian: I = 1%; C = 1%
Unknown: I = 1%; C = 1%
Comments about participants:
Patients were
stratified by type of
progression
(measurable vs PSA
alone), grade of
bone pain (mild,
moderate, severe,
disabling) and
SWOG
performance-status
(0–1 vs 2–3)
Drug reaction 0/0/3 0/0/3
Cardiovascular a
37/10/1 16/6/0
Clotting 2/0/0 0/0/0
Dermatological 1/0/0 1/0/0
Endocrine 0/0/0 1/0/0
Influenza-like 29/3/0 20/2/0
Nausea/vomiting a
61/5/0 16/1/0
Haematological 17/47/1 18/33/0
Haemorrhage 11/2/1 6/0/0
Immunological 3/0/0 0/0/0
Infection a
36/7/2 20/2/0
Liver 9/1/1 11/1/0
Lung 12/2/1 8/1/1
Metabolic a
14/6/0 2/0/0
Musculoskeletal 8/0/0 1/2/0
Neurological a
21/2/0 5/0/0
Pain 34/1/0 18/5/0
Renal/bladder 8/0/1 3/0/0
Max. grade of any a
114/62/8 63/46/4
Inclusion/exclusion criteria:
Pathologically confirmed adenocarcinoma
of the prostate and
progressive metastatic disease (stage
D1 or D2) despite androgen-ablative
therapy and cessation of antiandrogen
treatment
ITT analysis
performed: Yes
No. randomised: 384
(336 eligible)
Route of administration:
Mitoxantrone, i.v.;
prednisone, not reported
Dose: 12–14 mg/m 2
mitoxantrone
No. of cycles: 12
Length per cycle:
21 days
Per protocol
analysis
performed: Not
stated
Criteria for progressive disease were
progression of a bi-dimensionally
measurable lesion, as assessed within
28 days before study registration;
progression of disease that could be
evaluated but not measured (e.g. by
bone scanning), as assessed within
42 days before registration; or an
increase in serum PSA level over the
baseline level in at least two
consecutive samples obtained at least
7 days apart
Comments:
Baseline
comparability:
Adequate
Comments about
intervention/control:
a = p < 0.005.
The rate of grade 3, 4 or 5 neutropenia in the docetaxel
group did not differ significantly from that in the
mitoxantrone group (16.1% versus 12.5%; p = 0.22).
However, the docetaxel group had significantly higher rates
of grade 3 or 4 neutropenic fevers (5% versus 2%;
p = 0.01)
Protocol deviations:
Warfarin and aspirin were
added to the intervention
group due to a report that
prophylactic
anticoagulation decreased
estramustine-associated
vascular effects (15 January
2001). Numbers of
patients enrolled
Adequate renal, hepatic and cardiac
function and a SWOG performancestatus
score of 0–2 (3 was allowed if
due to bone pain) were also required
Patients were ineligible if they had
received prior radioisotope or
anticoagulant therapy (excluding
Eligibility criteria
specified: Yes
Co-interventions:
Premedication with
dexamethasone was
given in the
intervention group.
The intervention
group was also given
warfarin and aspirin
after a protocol
change on 15
January 2001. To
ensure continued
androgen ablation,
continued