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Home: PCU
1|2003: William Kevin Kelly, DO
Edited comments by Dr Kelly
CASE 4:
69-year-old man with metastatic disease following initial primary
treatment with brachytherapy and external beam radiation therapy
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History
On a routine visit in 11/98, the patient had a PSA of 7.3
ng/mL and normal exam. Prostate biopsy revealed adenocarcinoma
in both lobes of the prostate, Gleason 3+4 in seven out of
10 cores on the right and Gleason 3+5 in one out of six cores
on the left. CT and bone scans were negative. He was treated
with a combination of brachytherapy and external beam radiotherapy.
In 11/99, his PSA nadired to 1.38 ng/mL. His next PSA in
5/01 was 85.15 ng/mL, and the staging workup revealed metastatic
disease to the liver, multiple osseous metastases and extrinsic
compression of the rectum.
The patient was treated with combined androgen blockade,
his PSA decreased to 0.35 ng/mL, and his rectal obstruction
lessened. Within nine months his PSA rose to 5.49 ng/mL. The
antiandrogen was stopped and re-staging revealed progressive
disease in the liver and bone. He also had an asymptomatic
femoral vein thrombosis observed on CT, and we anticoagulated
him. At this point he was very fatigued, had right upper quadrant
pain and his performance status was 70% to 80%. We talked
about treatment options — palliation versus chemotherapy
versus an investigational approach. He wanted active treatment,
and we treated him with estramustine, paclitaxel and carboplatin,
which he tolerated very well. He’s now off pain medication,
more active and his quality of life has improved dramatically.
After completing his first two cycles of therapy, he had a
50% regression in liver lesions.
DISCUSSION
Patients with metastatic prostate cancer often respond well
to palliative chemotherapy, but typically these tumors come
back very quickly. This patient had significant improvement
in his quality of life after treatment.
We use a platinum-based regimen in patients like this with
high-grade tumors, because many of these high-grade tumors
have neuroendocrine features, which respond well to this regimen.
Patients with visceral metastases, particularly liver metastases;
low tumor burdens relative to PSA; and a short hormonal response
often have tumors with neuroendocrine features. |
Paclitaxel, estramustine and carboplatin for metastatic
prostate cancer
We recently reported results of this regimen, which was generally
welltolerated and showed significant anti-tumor activity. The major
complication was thromboembolic disease — usually deep venous
thrombosis — which occurred in approximately 25% of the patients.
Most of these patients were anticoagulated and continued on therapy
with no subsequent sequelae.
Nineteen of 24 patients who were being treated for severe pain
were able to discontinue narcotics. About two-thirds of the patients
had at least a 50% decline in PSA, and 45% of the patients had measurable
disease regression.
Chemotherapy for advanced prostate cancer
In a generally healthy man, my first-line chemotherapy choice
is usually an estramustine-taxane-based regimen — either estramustine-paclitaxel
or estramustine-docetaxel. These regimens are well tolerated, and
there is a lot of latitude in adjusting the dose if necessary.
There are toxicities so you have to select your patients carefully.
In patients who have severe cardiac disease or other comorbidities,
some of these regimens may not be optimal. On the other hand, response
to second-line chemotherapy in advanced prostate cancer is not very
good, and I usually try an investigational therapy at that point.
Trial randomizing to doxorubicin versus doxorubicin
plus samarium
There were 103 patients who received induction chemotherapy and
were then randomized to doxorubicin alone versus doxorubicin plus
samarium, using samarium for bone consolidation. Samarium was chosen
because it targets the bone and, subsequently, can target additional
cells that are within the bone stroma.
The results showed there was significant benefit in the patients
who received the bone-targeted therapy. The median survival was
increased from 16.8 months to 27.7 months. This was a significant
finding because we hadn’t seen any studies that actually showed
improvement in overall survival. Unfortunately, this is a small
study, but it’s interesting that we’re starting to use
combined modality therapies to treat prostate cancer, actually targeting
the end organs.
Chemotherapy regimens result in responses in about 70% of the patients,
but typically when the chemotherapy is stopped, the disease recurs
in three to four months. Often I’ll use this bone consolidation
approach after a patient’s had a response to chemotherapy,
looking for a way to stabilize the response. There are two radioisotopes
that can be used — strontium-89 and samarium. I’ll use
either, but samarium may be preferable because it has less bone
marrow toxicity than strontium. Repeated doses of strontium-89 result
in myeloablation, making it very difficult to treat the patient
with further chemotherapy.
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