| Tracks 1-12 |
| Track 1 |
SWOG-9346: Intermittent versus continuous combined androgen blockade with bicalutamide and goserelin in patients with metastatic prostate cancer |
| Track 2 |
Quality of life in men receiving continuous versus intermittent therapy |
| Track 3 |
Clinical presentation of newly diagnosed metastatic disease |
| Track 4 |
Combined androgen blockade with bicalutamide |
| Track 5 |
Clinical investigations of vaccines
for the treatment of advanced
prostate cancer |
| Track 6 |
Clinical trials evaluating docetaxel in advanced prostate cancer |
|
| Track 7 |
Use of docetaxel in patients with
hormone-refractory PSA-only
progression |
| Track 8 |
Risks and benefits of docetaxel in the treatment of metastatic disease |
| Track 9 |
Referral of patients with prostate
cancer to medical oncologists for
consideration of treatment with
chemotherapy |
| Track 10 |
Clinical trials of adjuvant
chemotherapy in early prostate
cancer |
| Track 11 |
EPC trials of bicalutamide as
adjuvant monotherapy |
| Track 12 |
Integration of medical oncologists
into the care of patients with
prostate cancer |
|
|
Select Excerpts from the Interview
Track 1
DR LOVE: Can you discuss the current clinical trials evaluating intermittent
hormonal therapy?
DR VOGELZANG: SWOG trial 9346, which evaluates intermittent versus
continuous hormone therapy in patients with metastatic disease, is a good trial.
We do not know how long it will take to learn the answer, but it continues to
be a burning question.
This study was designed in the late 1990s, and it has some significant methodological
flaws. It allows men to receive seven cycles or eight months of
hormone therapy for overt metastatic disease. Patients are then randomly
assigned to intermittent or continuous hormone therapy. If their PSA levels have
not dropped below 4 ng/mL, they are not allowed to be randomly assigned.
Maha Hussain’s ASCO abstract (Hussain 2006) provided us with striking
preliminary data with the PSA cutoff point at 4 ng/mL. That proved to be
smart because if their PSA levels did not go below 4 ng/mL after seven cycles
of hormone therapy, participants had a survival of less than 18 months. If
their levels went below 4 ng/mL but were still detectable, their survival was
approximately three years, and with undetectable levels, they had a survival
near 75 or 80 months. That’s a remarkable post-treatment prognostic factor.
I don’t know if intermittent versus continuous hormonal therapy will improve
on those three major categories. First, if your PSA level is 4 ng/mL or higher
after the first eight months of therapy, you will probably do badly whether you
receive intermittent or continuous therapy, and if your level is below 0.1 ng/mL
or undetectable, you will probably do well whether you receive intermittent or
continuous therapy. So in that later subset, intermittent therapy might win.
The other problem with the study is that it doesn’t define testosterone
recovery precisely. How long testosterone takes to recover after the first eight
months of therapy is not known. Perhaps it’s a function of age, with the older
men requiring longer times to recover.
Track 4
DR LOVE: In what situations, if any, do you use combined androgen
blockade?
DR VOGELZANG: I use this strategy routinely. I’ve considered the data many
different times and in different ways. The meta-analysis (PCTCG 2000)
shows that flutamide and nilutamide added to luteinizing hormone-releasing
hormone (LHRH) agonist therapy do bring a small but statistically significant
improvement in survival (Schmitt 2001). If you add cyproterone acetate to
leuprolide or orchiectomy, you see a decrement in survival. So the estrogenic
or progestational agents have a negative effect, and they’re not to be combined
with an LHRH agonist.
Bicalutamide has been studied in only one Japanese trial (Usami 2007), in
which it was administered at a dose of 80 milligrams. The trial showed a
remarkable improvement for the addition of bicalutamide to the LHRH
agonist. That’s the only study available of an LHRH agonist with or without
bicalutamide, although there are indirect studies suggesting that bicalutamide
conveys an advantage.
DR LOVE: What we’ve seen in our Patterns of Care studies and in talking
with clinical investigators is that this is not necessarily what’s done in practice.
Many don’t even discuss combined androgen blockade as an option with
patients because they are concerned about cost.
DR VOGELZANG: It’s true that I’ve become the minority. The guidelines were
written based on the flutamide and nilutamide data, which did not show
much of an advantage. If they’d read the fine print, they would have seen that
the slight benefit of flutamide and nilutamide (about a three to four percent survival difference at five years) is counterbalanced by the cyproterone acetate
data, and the bicalutamide data were not included (PCTCG 2000). I continue
to be a contrarian and prescribe bicalutamide regardless of the ASCO or AUA
guidelines.
Track 6
DR LOVE: What are some of the key studies being conducted right now
in metastatic disease?
DR VOGELZANG: ECOG has a trial underway called the CHAARTED
(ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for
Extensive Disease in prostate cancer) study (E3805), which moves docetaxel
earlier into the hormone-sensitive phase. They’re taking patients with poorer
risk, higher PSA levels and higher alkaline phosphatases with bone pain and
randomly assigning them to hormones versus hormones with chemotherapy
— in this case, docetaxel.
It’s a well-designed trial. The difficulty is that at least three trials have evaluated
hormones with or without chemotherapy in the past, which have not
shown an advantage to adding the chemotherapy. Granted it was “old-line”
chemotherapy with CMF. So the CHAARTED study has a reasonable chance
of showing an improvement in survival with the addition of docetaxel at the
hormone-sensitive rather than the hormone-resistant phase.
DR LOVE: Are there any situations outside of a protocol setting in which you
might start chemotherapy when hormone therapy was being initiated?
DR VOGELZANG: I have used it when patients have overtly poor-risk disease
(Figure 3.1, examples of trials incorporating docetaxel in the treatment of
high-risk prostate cancer). A classic situation is when PSA fails to normalize
after radical prostatectomy. Patients will commonly have nodal metastases,
seminal vesicle involvement or positive margins. I have recommended
docetaxel with hormone therapy for a handful of patients at that point.
Track 8
DR LOVE: Can you put in perspective what docetaxel brings to the
patient being treated for hormone-refractory metastatic disease?
DR VOGELZANG: Docetaxel has been a hugely beneficial drug for patients
who have painful bone metastases from prostate cancer. Without question,
this drug benefits a substantial majority (80 to 85 percent) of patients, and the
benefit for some of these patients lasts for two years or more. So the urologist
and the radiation oncologist should feel comfortable endorsing the drug as a
safety net if hormonal therapy fails.
DR LOVE: What do you tell a patient to expect in terms of quality of life with
docetaxel?
DR VOGELZANG: If patients starting on docetaxel have a PSA level of 40
or 50 ng/mL, retroperitoneal nodes and maybe a few bone lesions, they do
extremely well. They are not sick. They can work almost every day except for
the day of chemotherapy. They receive prednisone with the docetaxel, so they
experience no nausea.
The biggest problems are nail changes — some cracking or curling. However,
there’s not much leukopenia, thrombocytopenia or anemia. There’s no real
organ toxicity. It’s extremely rare to see a pulmonary complication, so the
drug is easy to administer.
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