| Tracks 1-15 |
| Track 1 |
Introduction |
| Track 2 |
Clinical trial of adjuvant docetaxel/
prednisone for high-risk disease
after prostatectomy |
| Track 3 |
Efficacy and toxicity of adjuvant
docetaxel/prednisone |
| Track 4 |
Fatigue, alopecia and GI toxicity
associated with docetaxel/
prednisone |
| Track 5 |
Improvement in time to PSA
relapse in a pilot study of adjuvant
docetaxel for patients with high-risk
disease |
| Track 6 |
Immediate versus deferred
adjuvant leuprolide with or
without docetaxel for patients at
high risk of relapse after
prostatectomy |
| Track 7 |
Clinical and biochemical
progression as trial endpoints |
|
| Track 8 |
Immediate versus delayed
hormonal therapy |
| Track 9 |
Use of chemotherapy for patients
with hormone-refractory, PSA-only
disease |
| Track 10 |
Prostate cancer as a
chemotherapy-sensitive disease |
| Track 11 |
Novel therapeutic strategies in
prostate cancer |
| Track 12 |
Utilization of PSA doubling time in
treatment decision-making |
| Track 13 |
Potential role of bevacizumab
in the management of prostate
cancer |
| Track 14 |
Role of medical oncologists
in advancing prostate cancer
research |
| Track 15 |
Developing agents targeting the
androgen receptor |
|
|
Select Excerpts from the Interview
Tracks 2-5
DR LOVE: Can you talk about the new clinical trial of adjuvant docetaxel
for patients following prostatectomy (3.1)?
DR EISENBERGER: This is a trial for patients with high-risk features following
radical prostatectomy — positive seminal vesicles, a high Gleason score,
positive nodes, disease outside the gland or positive margins. These patients
will be randomly assigned to receive adjuvant docetaxel and prednisone
every three weeks for six cycles (3.1) — just as on TAX-327 (Tannock 2004)
— versus placebo. The endpoint is time to PSA progression.
We are also currently conducting a trial evaluating androgen deprivation with
or without chemotherapy versus observation (3.2). This is a fascinating study
of men who present with high-risk features, and we quantify them by using
Mike Kattan’s nomogram (Kattan 1999). Eligible patients have less than a 60
percent chance of remaining disease free at five years.
In general, the patients have a high Gleason score, more than eight positive
seminal vesicles, positive margins, positive nodes and disease outside of the
gland. They must have an undetectable PSA level following radical prostatectomy,
and that is measured somewhere between two to three months afterward.
The patients are then eligible for study entry and are randomly assigned
between androgen deprivation therapy alone or androgen deprivation with
chemotherapy or observation.
Patients on the observation arm receive treatment at the time of progression.
Treatment on both arms consists of either 18 months of hormonal therapy
with leuprolide or 18 months of hormonal therapy with leuprolide and
docetaxel given for six cycles, now using the every three-week schedule.
The study is two-by-two factorial in design, and we’re evaluating the contribution
of chemotherapy to hormonal therapy. The only complication is that
it’s not a survival study. In prostate cancer, a survival study would require
many years and a study with more than 5,000 patients.
DR LOVE: You conducted a pilot study of adjuvant chemotherapy for men
with high-risk disease. Can you talk about the design of that trial?
DR EISENBERGER: The pilot study (Rosenbaum 2005, 2006) was started in
2002. We used Mike Kattan’s nomogram, which estimates the probability
of PSA relapse based on clinical and pathological features. Men with high-risk features received six months of adjuvant docetaxel with prednisone, no
androgen deprivation, and the trial was fascinating. We finished the trial six
months ahead of time, with 77 patients.
DR LOVE: What specifically did you see in terms of antitumor effects and side
effects and toxicity?
DR EISENBERGER: We used the weekly docetaxel because we didn’t have
the TAX-327 data yet. So there were eye problems, nail toxicity, alopecia and
fatigue. Of the 77 patients, 76 completed treatment.
The one man who did not complete it was a construction worker. He was a
little fatigued and was missing work, so he couldn’t continue it, but he had no
significant toxicities.
In general, when we conduct a pilot study, we include patients with advanced
disease. For example, in the adjuvant chemotherapy pilot study, we did not
require patients to have an undetectable PSA level following radical prostatectomy.
So about half the patients had measurable PSA levels following radical
prostatectomy, and the pathological staging was advanced in these patients.
Many patients had positive nodes and positive margins. In that subset of
patients, the predicted median time to PSA relapse was only 10 months.
However, the observed time to PSA relapse in the pilot study was almost 20
months, and we have some men who have not relapsed yet.
It’s quite interesting and quite encouraging, but obviously that observation
must be taken with a grain of salt.
Track 9
DR LOVE: In the patient who has hormone-refractory disease but still
has PSA-only disease, do you think that chemotherapy off protocol is a
consideration?
DR EISENBERGER: It’s a great question. I proposed a study to ECOG for men
with nonmetastatic disease who were treated with early hormonal therapy
and had a rising PSA. The question was what to do with these patients. The
standard approach out in the community today is second-line and third-line
sequential hormonal therapies.
DR LOVE: Often, when patients complete second- and third-line therapies,
they still have PSA-only disease.
DR EISENBERGER: Yes, they still have PSA disease, and they have it for many
years. That’s what the data have shown, but some men have poor outcomes
in this group, which provides a great opportunity to evaluate chemotherapy.
ECOG-E1899 (Walczak 2003) asked that question, but we had to stop accrual.
We hope to come back and address that question again some time in the
future.
Track 10
DR LOVE: Have you seen patients with PSA-only disease who have
obvious and significant drops in PSA just from chemotherapy?
DR EISENBERGER: Yes, studies show the response to chemotherapy alone
without androgen deprivation is greater than 50 percent.
DR LOVE: Some oncologists consider prostate cancer relatively refractory to
chemotherapy compared to other solid tumors like breast and colon cancer. Do
you agree?
DR EISENBERGER: I do not. In 1985, during the pre-PSA era, I wrote a paper about chemotherapy for hormone-refractory prostate cancer (Eisenberger
1985). The study endpoint was survival, and responses were low.
Why do we see a difference now? One of the main reasons is that we now see
a different man with prostate cancer compared to before — the PSA provides
us with enormous lead time, so we’ve seen a major stage migration.
And along with the generally better condition of patients with metastatic
prostate cancer now, we’re dealing much more with the biology of these
diseases, which includes susceptibility to chemotherapy. I believe prostate
cancer patients are as sensitive to chemotherapy as patients with other solid
tumors that are considered responsive.
Select publications
