|
CASODEX 50 mg - Where Does It Fit In?
(April 2003)
Recently I was asked to sit in with a
prostate support group and I listened as the men recounted the various
treatments they were currently receiving. One man indicated that when his
PSA commenced to rise following initial Lupron he was prescribed Casodex,
50 mg daily. This raised in my mind the question of the strength of
evidence for that dosage. I have been surprised how little data is
available to answer that question.
In the life and death chess match against the androgen receptor the
initial move in response to the first rise of PSA post primary therapy is
some form of androgen deprivation. Even the grand chess master Bobby
Fisher would open with "Lupron" to "king pawn 3". But other choices are
equally acceptable: Zoladex, castration, DES 1 mg/qd, Abarelix (when
available and after some additional testing). All
of these decrease the testosterone level to < 50 ng/dL. Castration usually
results in a testosterone value of < 20 ng/dL. Casodex at 150 mg.
daily, however, raises serum testosterone. The additional options of Casodex 50 mg + Proscar 5-10 mg are also effective despite often raising
the testosterone level. Combined androgen blockade (CAB) with an LHRH
agonist/antiandrogen was initially reported to provide a survival benefit
compared to LHRH monotherapy. Dr. David Crawford's early report indicated
a 26% survival advantage for CAB (28.3 vs.35.6 months, P=.35). However,
the most recent meta-analyses estimate the benefit at between 1.8% or
slightly more. The current National Comprehensive Cancer Network guideline
(www.nccn.org) for prostate cancer management makes the interesting
suggestion: if monotherapy with an LHRH agonist is initiated, the
testosterone level should be checked in several months. If castrate level
has not been achieved, then an antiandrogen "may be added".
Casodex (and Flutamide) functions as a competitor to testosterone and
dihydrotestosterone for the androgen receptor, and it's effectiveness is
dose dependent. A 1998 study compared Casodex at doses between 10 and 200
mg daily for 12 weeks in treatment of advanced PC. The median percentage
decrease in PSA for the 50 mg, 100 mg, and 200 mg doses were 90%, 93.4%,
and 94.8% respectively. Casodex 50 mg/qd is not recommended as primary
hormonal intervention based on the data from a 1996 Swedish cooperative
study which found an inferior survival for the 50 mg dose of Casodex
compared to castration, whereas 150 mg/qd is equivalent to castration in
this setting.
The most common point of intervention with second line hormonal therapy,
however, is in the setting of a rising PSA post LHRH agonist in patients
with either minimal or no evidence of metastases - and this is the
situation where the data is skimpy. The best data comes from a SWOG study
presented only in abstract form in the ASCO 1997 Proceedings (#116) in
which 27 men with rising PSAs received Casodex 50 mg/qd (19 with a
positive bone scan, 8 with only a rising PSA). The median time to
progression was 53 days (range 8 - 292) with 14 men showing progression
within two months.
Because of the minimal benefit of the 50 mg dose, SWOG carried out a
second study using a 150 mg/qd dose. This was reported in UROLOGY 2001,
July. This trial involved 52 men with advanced PC, 69% with bone
metastases and an additional 8% with soft tissue disease only. The means
PSA on entry was 107. 20% showed a PSA decrease of > 50%; 32% had stable
disease; some experienced palliative benefit; and the median survival was
15 months. One of the hazards
of extrapolating from both the SWOG studies arises from the inclusion in
both by large component of men with substantially advanced metastatic
disease. If antiandrogen therapy were introduced earlier, there might not
have been an improved "response", but the survival times would have been
lengthened because of "lead time bias".
Studies have shown that Casodex can effect responses after Flutamide
usage. When Casodex 150 mg/qd was used after primary androgen deprivation
(CAB) with a LHRH agonist plus Flutamide responses occurred in 43%.
Casodex therapy was not initiated until there was further PSA failure in
the 40% that showed a "flutamide withdrawal response". When Flutamide was
used post LHRH/Casodex (50 mg) treatment the response was only 6%. Other
studies have recorded responses in the range of 20% to 38% to Casodex
after Flutamide usage - especially in instances of Flutamide failure after
initial response.
Bottom Line: Casodex 50 mg/qd offers only minimal benefit as second line
hormonal intervention.
«
Back to Article List
|
