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

TABLE 2 Treatment comparisons
relative effectiveness of docetaxel versus best
supportive care.
The following sections describe the results of each
individual study. Following this, an attempt is
made to synthesise these data using narrative and
formal quantitative approaches.
Clinical evidence
Docetaxel plus prednisone versus
mitoxantrone plus prednisone
One RCT (TAX 327) was identified which aimed
to determine whether docetaxel plus prednisone
improves overall survival compared with
mitoxantrone plus prednisone in men with
advanced mHRPC. In addition to the main
publication of the trial, 27 there were two
abstracts, 35,36 an approval package 37 and an
approval summary 34 from the Center for Drug
Evaluation and Research at the FDA. A further
report was obtained from Sanofi-Aventis as part of
the industry submission. 61
Description of the trial comparing docetaxel plus
prednisone with mitoxantrone plus prednisone
This multi-centre RCT included 1006 men with
mHRPC; 335 patients were randomised to receive
a 1-hour intravenous infusion of docetaxel
(75 mg/m 2 on day 1 every 21 days) plus oral
prednisone (or prednisolone), herein referred to
as the 3-weekly docetaxel group, 334 patients were
randomised to receive a 30-minute intravenous
infusion of docetaxel (30 mg/m 2 on days 1, 8, 15,
22 and 29 in a 6-week cycle) plus oral prednisone
(or prednisolone), herein referred to as the weekly
docetaxel group, and 337 patients were
randomised to receive a 30-minute intravenous
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Health Technology Assessment 2007; Vol. 11: No. 2
Treatment comparisons
Trial D a + P D a + P + E D + E M + C M + C + Clo C
TAX 327 ✓ ✓(M+P)
Oudard et al. ✓ ✓(M+P)
SWOG 9916 ✓ ✓(M+P)
Berry et al. ✓(M+P) ✓(P)
CCI-NOV22 ✓(M+P) ✓(P)
CALGB 9182 ✓(M+H) ✓(H)
Ernst et al. ✓(M+P) ✓
C, corticosteroid (either prednisone or hydrocortisone); Clo, clodronate; D, docetaxel; E, estramustine; H, hydrocortisone;
M, mitoxantrone; P, prednisone/prednisolone.
a Evaluated at two different dosages.
infusion of mitoxantrone (12 mg/m 2 on day 1 every
21 days) plus oral prednisone (or prednisolone),
herein referred to as the mitoxantrone group.
Patients in the docetaxel groups also received
premedication with dexamethasone. Patients were
stratified by baseline pain level and Karnofsky
performance-status score. The baseline
characteristics of patients across the three groups
appear to have been well balanced in terms of
Gleason score, PSA level, presence of pain,
performance status, evidence of progression at
entry (bone scan, increase in lesions or PSA),
previous treatments, age, extent of disease, race
and stage of disease at diagnosis.
For inclusion in the trial, patients had to have
clinical or radiological evidence of metastatic
disease with disease progression during hormonal
therapy; an increase in serum PSA level on three
consecutive measurements obtained at least 1 week
apart or evidence from physical examination or
imaging studies. Patients were also required to
have a Karnofsky performance-status score of at
least 60% and stable levels of pain for at least
7 days before randomisation; daily variation of no
more than one in Present Pain Intensity (PPI) scale
from the McGill–Melzack questionnaire or 25% in
analgesic score.
The median number of cycles received by the
3-weekly docetaxel group was 9.5 (range 1–11),
the median number received by the group
receiving weekly docetaxel (6-week cycle) was 4
(range 1–6) and the median for the mitoxantrone
group was 5 (range 1–11). The planned treatment
was delivered to 98% patients in the 3-weekly
docetaxel group, 96% in the weekly docetaxel
group and 99% in the mitoxantrone group. The
proportion of patients in each of the groups
15