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
Multivariate analysis of baseline factors and palliative
response (from Dowling et al. 45 ):
treatment was delayed
until levels were exceeded
Other participant characteristics:
ECOG performance status:
thereafter. A daily
analgesia diary was
also kept by patients
Variable p OR (95% CI)
Control: Prednisone
Status I: n (%) C: n (%)
Older age 0.07 1.02 (0.99 to 1.05)
Increasing ECOG 0.005 1.44 (1.12 to 1.85)
Increasing pain 0.0008 1.46 (1.17 to 1.81)
Increasing haemoglobin 0.02 0.99 (0.98 to 0.99)
Increasing alkaline phosphatase 0.07 1 (1 to 1)
Palliative response 0.11 0.74 (0.51 to 1.07)
No. randomised: 81
Route of administration:
orally
Dose: 5 mg b.d.
0 5 (6) 3 (4)
1 45 (57) 47 (59)
2 21 (26) 22 (28)
3 8 (10) 8 (10)
Unknown 1 (1) 1 (1)
No. of cycles:
Method of
randomisation:
Assignment/
allocation: Not
reported (stratified
by ECOG score:
0, 1 vs 2, 3).
Length per cycle:
Present pain intensity
Outcome 2: Progression-free survival
From Center for Drug Evaluation and Research20 (response
based on primary criterion only)
Score I: n (%) C: n (%)
ITT analysis
performed: Yes
Responders (N = 33):
I, n = 23; C, n = 10
Median time to progression (N = 147):
I, 301 days; C, 133 days; p = 0.0001
(relationship remained when controlling for baseline
performance status and PPI score)
Comments about
control group: Nonresponding
patients or
those with progressive
symptoms after treatment
for ≥ 6 weeks were
crossed over to I. 50 (62%)
patients crossed over –
this was reported as 48
elsewhere
0 1 (1) 1 (1)
1 30 (38) 23 (28)
2 30 (38) 37 (46)
3 15 (19) 15 (19)
4 4 (5) 5 (6)
Per protocol
analysis
performed: Not
stated
Analgesic score: median (interquartile
range)
I, 18 (10–30); C, 14 (6–24)
Non-responders (N = 128, data available for 114):
I, n = 54; C, n = 60
Median time to progression:
I, 70 days; C, 54 days; p = 0.0116
Median time of crossover
was at 84 days (range:
11–324 days)
Overall QoL (LASA scale;
0 = extremely ill–10 = feel well):
median (Interquartile range)
I, 5.9 (4.7–8.1); C, 6.5 (4.8–8.0)
Comments: Power
calculations required
a sample size of 150.
For PSA sensitivity
analysis patients with
missing data are
considered nonresponders
(from
Dowling et al. 45 )
All patients (N = 147):
I, n = 77; C, n = 70
Treatment failures:
I, 43; C, 60
Median time to progression:
I, 148 days; C, 62 days, p = 0.0001
Outcome 3: Response rate
Palliative response, primary outcome of paper (defined as
2-point reduction in the PPI scale, or complete relief if
1+ initially, without an increase in analgesic score maintained
on 2 consecutive visits at least 3 weeks apart) (N = 161):
I: 23/80 (29%; 95% CI: 19 to 40%)
Patients still responding
after a cumulative dose of
140 mg/m 2 mitoxantrone
were crossed over to C to
minimise probability of
cardiac toxicity
Overall QoL (EORTC QLQ-C30; 0
= very poor–100 = excellent):
median (interquartile range)
I, 46 (33–58); C, 50 (33–58)
Protocol deviations:
Halfway through study
withdrawal responses to
flutamide were
recognised; patients then
evaluated for ≥ 4 weeks
after stopping flutamide
Comments about participants:
Baseline
comparability:
Trend for patients
randomised to I to
have a higher
analgesic score and
to be treated with
flutamide
Inclusion/exclusion criteria:
Metastatic adenocarcinoma of the
prostate, with symptoms that
included pain and disease progression
despite standard hormonal therapy.
ECOG score ≥ 3
Eligibility criteria
specified: Yes
continued