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Prostate Cancer
Therapeutic Approach to Hormone-refractory Prostate Cancer
a report by
Fred Saad
Director of Urologic Oncology, Chair in Prostate Cancer and Full Professor of Surgery/Urology, University of Montreal
Prostate cancer is the most common cancer in North American males regimen was subsequently approved for HRPC based on palliative
and the third leading cause of death due to cancer. However, since the benefit. Subsequently, in 2004, docetaxel plus estramustine was
introduction of androgen deprivation therapy (ADT) in the 1940s, compared with mitoxantrone plus prednisone every three weeks, and
there have been few meaningful therapeutic advances. Palliative this trial demonstrated the first survival benefit in this patient
chemotherapy with mitoxantrone and prednisone was introduced in population.
7
Median survival was increased by two months (p=0.01) in
1996, zoledronic acid in 2002 and docetaxel in 2004. Although patients treated with docetaxel plus estramustine. A significant
docetaxel is the first agent to demonstrate a survival advantage in this increase in PSA response (p<0.0001) was also observed in the
setting, improving survival may not be feasible in many elderly prostate docetaxel plus estramustine group. There was, however, significant
cancer patients who cannot tolerate chemotherapy. ADT has been, added toxicity due to estramustine.
and continues to be, the most common treatment for men with
advanced prostate cancer, and is now used earlier in the continuum of A similar international trial comparing two schedules of docetaxel
care for prostate cancer (before bone metastases develop) based on (either every three weeks or weekly) plus prednisone, versus
rising prostate-specific antigen (PSA) following primary therapy. Earlier mitoxantrone plus prednisone for 30 weeks demonstrated a significant
use has been shown to improve survival and delay bone metastasis. 2.5-month survival advantage (p=0.009) in patients treated with
However, ADT is associated with adverse effects such as fatigue, docetaxel (every three weeks) compared with the mitoxantrone plus
depression, increased fat mass, loss of libido and hot flushes. In prednisone group.
8
In contrast, docetaxel plus prednisone administered
addition, recent evidence has demonstrated that ADT is often weekly did not demonstrate a significant improvement in survival.
associated with bone loss.
1
Docetaxel plus prednisone also significantly improved pain response
and PSA response rates compared with mitoxantrone plus prednisone
Bone loss in patients with prostate cancer may be attributed to the (p=0.01 and p=0.0005, respectively). In general, docetaxel was well
disease itself – which is a risk factor for osteoporosis – and to ADT. Bone tolerated. Grade 3/4 toxicities included neutropoenia, with 3% of the
loss associated with ADT has been shown to increase the risk of patients in the docetaxel (every three weeks) group being hospitalised
fractures.
2,3
Moreover, approximately 70% of patients with advanced with febrile neutropoenia compared with 2% of the patients in the
prostate cancer will develop bone metastases, which cause local mitoxantrone plus prednisone group. Common non-haematological
decreases in bone integrity. All of these disease-associated factors lead adverse events included alopecia, fatigue and nausea. By significantly
to a fragile bone state and a significant risk of skeletal complications, improving survival and reducing both PSA and pain levels, docetaxel has
including pathological fractures, debilitating bone pain and spinal cord now become the first-choice chemotherapy in HRPC.
compression. The patient’s quality of life (QoL) is affected by these
complications. Therefore, symptom control and maintaining QoL are Bone-targeted Therapy
priorities for patients with hormone-refractory prostate cancer (HRPC).
4,5
Radiation/radioisotope therapy and bisphosphonates are palliative
Treatment of Hormone-refractory Prostate Cancer
Treatment options for patients with metastatic HRPC include second-
Fred Saad is Director of Urologic Oncology, Chair in
Prostate Cancer and Full Professor of Surgery/Urology at
line hormonal manipulations, chemotherapy, bisphosphonates and/or
the University of Montreal. Previous positions include Chief
radiation/radioisotope therapy to reduce skeletal morbidity. Second-
of Urology at Notre-Dame Hospital of the University of
Montreal. Dr Saad established the first urological oncology
line hormonal manipulation may sometimes temporarily lower PSA
clinic and research centre at the University of Montreal. His
levels, but these regimens have not been shown to improve survival. It main research interests include molecular prognostic
is now the standard of care to stop anti-androgens when patients
markers and hormone-refractory prostate cancer, and he is
currently co-ordinating over 30 clinical and basic research
progress onto hormone therapy. Whether there is any clinical benefit
projects in urological oncology. Dr Saad was President of the Quebec Urologic Association
to changing anti-androgens or increasing the dose of a given anti-
from 2001 to 2003. He is Secretary/Treasurer of the Executive Committee of the National
Cancer Institute of Canada Genito-urinary Group and the Canadian Urologic Oncology
androgen remains unknown.
Group (CUOG), and is a Member of the Canadian Prostate Health Council. In addition, he
sits on nine editorial boards and serves as a reviewer for over 20 urology and oncology
Chemotherapy
journals. He has published over 70 articles in peer-reviewed journals, has over 250
published abstracts and has been an invited speaker/professor over 200 times in 20 different
In 1996, chemotherapy (mitoxantrone plus prednisone) demonstrated
countries. Dr Saad obtained his medical degree in 1985 from the University of Montreal
significant palliative benefits in HRPC, significantly reducing
before completing a residency in urology in 1990. He then went on to undertake a
fellowship in urological oncology in 1992.
pain (p<0.0001) and improving QoL compared with prednisone
alone.
6
However, overall survival was not improved. This treatment
© TOUCH BRIEFINGS 2007 23
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