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

TABLE 8 Summary results table for docetaxel plus estramustine versus mitoxantrone plus prednisone
appear to have been well balanced in terms of
tumour characteristics, performance status,
previous treatments, age, sites of secondary
disease, race and stage of disease at diagnosis.
However, there was a tendency for the patients in
the mitoxantrone group to have a lower serum
PSA level at baseline than those in the prednisone
group.
For inclusion in the trial, patients had to have
asymptomatic hormone-refractory
adenocarcinoma that had progressed on at least
one hormonal regimen. Disease progression was
defined as two-fold or greater increase in PSA over
two measurements, 25% increase in number of
bone scan lesions or 25% increase in size of soft
tissue lesions. Patients were also required to have
adequate liver and cardiac function and an ECOG
performance status between 0 and 2 to be eligible
for inclusion in the trial. No crossovers were
allowed in the trial; however, administration of
prednisone was continued after mitoxantrone
therapy was discontinued.
CCI-NOV22 31
This multi-centre RCT included 161 men with
mHRPC; 80 patients were randomised to receive
an intravenous infusion of mitoxantrone
(12 mg/m 2 every 21 days) plus 5 mg of oral
prednisone twice per day, herein referred to as the
mitoxantrone group, and 81 patients were
randomised to receive 5 mg of oral prednisone
twice per day, herein referred to as the prednisone
group. Mitoxantrone therapy was continued until
a cumulative dose of 140 mg/m 2 was attained.
Dexamethasone and other steroid use were not
permitted. Patients were stratified by performance
status.
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Health Technology Assessment 2007; Vol. 11: No. 2
Docetaxel group Mitoxantrone group Comparison
Mortality 217/338 (64%) 235/336 (70%) HR = 0.80 (95% CI: 0.67 to 0.97)
Progression-free survival 312/338 (92%) 311/336 (93%) HR = 1.30 (95% CI: 1.11 to 1.52)
Response rate 17/103 (17%) 10/93 (11%) RR = 1.54 (95% CI: 0.74 to 3.18)
QoL response Not reported
Pain response No significant difference – data not
shown
PSA decline 155/309 (50%) 82/303 (27%) RR = 1.85 (95% CI: 1.49 to 2.30)
Adverse events:
Discontinued 54/330 (16%) 32/328 (10%)
Grade 3/4 176/330 (53%) 109/328 (33%)
Died 8/330 (2%) 4/328 (1%)
The baseline characteristics of patients across the
two groups appear to have been well balanced in
terms of age, sites of metastases, time since
diagnosis, ECOG performance status, PPI pain
score and overall QoL. However, there was a
tendency for the patients in the mitoxantrone
group to have a higher serum PSA level, higher
analgesic score and to have been treated with
flutamide compared with the patients in the
prednisone group.
For inclusion in the trial, patients had to have
metastatic adenocarcinoma of the prostate with
symptoms including pain and disease progression
despite standard hormonal therapy. Patients were
also required to have an ECOG performance
status score of 3 or better, with a life expectancy of
at least 3 months and the ability to complete pain
and QoL questionnaires. Non-responding patients
or those with progressive symptoms after
treatment with prednisone alone for 6 weeks or
more were allowed to cross over and receive
mitoxantrone in addition to prednisone.
The median cumulative dose of mitoxantrone
delivered was 73 mg/m 2 (range: 12–212 mg/m 2 ).
The median number of cycles of mitoxantrone was
6.5 (range: 1–18), with a median dose of 12 mg/m 2
(range: 5.1 to 16.5 mg/m 2 ) of mitoxantrone per
cycle. Mitoxantrone therapy was delayed for one
or more cycles in seven (9%) patients originally
randomised to receive mitoxantrone therapy. Of
the 81 patients randomised to receive prednisone
alone, 50 subsequently crossed over to receive
mitoxantrone in addition to the prednisone; five
(10%) of these patients required a delay in
mitoxantrone treatment. The median number of
days before crossing over was 84 days (range:
25