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

Effectiveness of mitoxantrone plus prednisone
plus clodronate versus mitoxantrone plus
prednisone plus placebo
Overall survival
Overall survival was defined as the time from the
date of randomisation to the date of death or
censored at the date when patient was last known
to be alive. Eighty-seven of the 104 patients in the
clodronate group and 89 of the 105 patients in the
placebo group died. The HR for death (placebo to
clodronate) was 0.95 (95% CI: 0.71 to 1.28). The
median overall survival was 10.8 months (95% CI:
8.2 to 13.0) in the clodronate group and
11.5 months (95% CI: 8.8 to 14.4) in the placebo
group.
Overall survival was statistically significantly
associated with a baseline haemoglobin level of
more than 100 g/l compared with those with a
baseline haemoglobin level of less than 100 g/l:
the HR for death was 0.52 (95% CI: 0.35 to 0.78;
p = 0.001).
Progression-free survival
Symptomatic progression-free survival was defined
as the time from randomisation to the date of
progression (pain or other symptoms), or date of
death for those who died without progression.
Ninety-five patients in the clodronate group and
101 patients in the placebo group developed
progression. The HR of developing progression
(placebo to clodronate) was 1.24 (95% CI: 0.93 to
1.64). The median symptomatic progression-free
survival was 5.0 months (95% CI: 4.1 to 6.8) in the
clodronate group and 4.0 months (95% CI: 2.9 to
4.9) in the placebo group.
Symptomatic progression-free survival was
statistically significantly associated with a baseline
haemoglobin level of more than 100 g/l compared
with those with a baseline haemoglobin level of
less than 100 g/l: HR = 0.67 (95% CI: 0.46 to
0.99; p = 0.04).
Response rate
Palliative response was the primary end-point for
the trial, defined as either a 2-point reduction in
PPI without an increase in analgesic score or
evidence of disease progression, or more than 50%
decrease in analgesic score without an increase in
PPI, on two consecutive evaluations at least
3 weeks apart. There was no statistically significant
difference in palliative response rate between the
clodronate group and the placebo group (43
versus 37.5%, p = 0.52). This gives an RR for
response of 1.14 (95% CI: 0.81 to 1.59). However,
when looking at the subgroup of patients with a
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Health Technology Assessment 2007; Vol. 11: No. 2
baseline PPI score of 3 or 4 (moderate pain), as
opposed to 1 or 2 (mild pain), the difference in
palliative response rate between the clodronate
group and the placebo group was statistically
significant [58 versus 26%, odds ratio (OR) for
palliative response for the clodronate arm
compared with the placebo arm = 4.6, p = 0.04].
The median duration of palliative response was
6.2 months (95% CI: 5.0 to 9.2) for the clodronate
group and 6.4 months (95% CI: 4.0 to 9.6) for the
placebo group; the difference was not statistically
significant.
Health-related quality of life
HRQoL response was defined as a 1-cm
improvement on a 10-cm visual analogue scale,
maintained on two consecutive visits, no less than
3 weeks apart. There was no statistically significant
difference in HRQoL response between the
clodronate group (37.5%) and the placebo group
(42%). This gives an RR for QoL of 0.89 (95% CI:
0.64 to 1.25).
Pain
Pain was assessed using the PPI scale from the
McGill–Melzack questionnaire. Scores range from
0 to 5, with higher scores indicating more pain.
Analgesic use was assessed using a diary and an
analgesic score was calculated by assigning a score
of 1 for a standard dose of non-opioids and a
score of 2 for opioid doses of morphine 10 mg
equivalents. Pain response was defined as a
2-point or more reduction in PPI score in
comparison with baseline, irrespective of
analgesic response. Analgesic response was
defined as a 50% or more decrease in analgesic
score from baseline with no increase in pain.
There was no statistically significant difference in
pain response or analgesic response between the
clodronate group (33% pain response, 33%
analgesic response) and the placebo group (26%
pain response, 30% analgesic response); giving an
RR for pain response of 1.27 (95% CI: 0.83 to
1.95). About 31% of patients in the clodronate
group no longer required analgesics for two
consecutive cycles, compared with 25% in the
placebo group; again, the difference was not
statistically significant.
PSA decline
PSA response was defined as a 50% or more
reduction from baseline in serum PSA levels for at
least two visits. Thirty patients in the clodronate
group had a PSA response (29.7%) compared with
30 patients (28.6%) in the placebo group; giving
an RR for PSA decline of 1.04 (95% CI: 0.68
to 1.59).
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