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Metastatic Prostate Cancer

Posted Aug 24 2008 1:49pm
ANNOUNCER: When disease returns after a man has been treated for prostate cancer, hormonal therapy is usually effective. This involves the removal of the testicles to shut down the production of testosterone. Or the use of drugs that have the same effect.

JAMES A. EASTHAM, MD: Traditionally, the approach to advanced disease has been hormonal therapy. Prostate cancer is driven by the male hormone testosterone. So by taking testosterone away, in many ways, you stop one of the promoting factors for cancer growth.

ANNOUNCER: Hormonal therapy, however, is likely to fail after a period of time. Tumors will eventually spread to bone or soft tissue. The first sign of the return of advanced disease is likely to be a rise in blood levels of a protein called PSA, which signals tumor growth and resulting damage to the prostate.

DANIEL P. PETRYLAK, MD: In the advanced prostate cancer patient, the median duration of response to hormones is generally about 18 to 24 months.

The first evidence that a patient is failing hormone therapy is usually a rise in the PSA. This usually precedes changes in the tumor that we can visually see on a bone scan or a CAT scan.

JAMES A. EASTHAM, MD: When someone has a rising PSA despite being on hormonal therapy, there are several additional hormonal manipulations or hormonal changes that can be made. If a patient is on what is called an antiandrogen, which is a medicine that actually blocks testosterone from binding its binding site or receptor, you can manipulate that. You can actually stop the antiandrogen.

DANIEL P. PETRYLAK, MD: There is almost a paradoxical withdrawal effect by stopping these medications, we sometimes, in about 20 to 30 percent of patients, see a PSA decline.

ANNOUNCER: But even among those patients, the effect will likely be temporary. At this stage, depending on a variety of factors, a patient may have only one or two years to live. Doctors traditionally could do little beyond helping prevent bone fractures, and managing pain. And there wasn't much of a role for chemotherapy in prostate cancer, until recently.

JAMES A. EASTHAM, MD: Probably the initial advance in chemotherapy was a drug called mitoxantrone, which, while it did not prolong survival, did help with symptoms of pain. And men who were on the drug had greater pain relief than men who did not receive mitoxantrone.

More recently, the taxanes, primarily Taxotere, which is a chemotherapy drug, has been shown to actually not only help with pain, but also prolong survival in prostate cancer. Again, these are men with advanced, what we would call hormone refractory prostate cancer.

DANIEL P. PETRYLAK, MD: When taxane-based chemotherapy is compared to the previous standard of care, which had been mitoxantrone combined with prednisone, there is a 20 to 24 percent improvement in the overall survival in patients treated with a taxane.

ANNOUNCER: That translates to a modest average increase in life. But among men with advanced disease that has stopped responding to hormonal therapy, a small gain can mean a lot.

JAMES A. EASTHAM, MD: The survival advantage in the large clinical trials looking at Taxotere showed a modest benefit, probably in the range of two to three months. While that doesn't sound like a prolonged period of time, life expectancy in this group of men with advanced prostate cancer is only about 14-16 months. So an extra two to three months is actually significant.

ANNOUNCER: The problem of side effects remains, especially since these men are quite ill. But doctors say few men actually stop chemotherapy.

DANIEL P. PETRYLAK, MD: There does seem to be a higher frequency of side effects with docetaxel-based therapy and these include drops in white blood cell counts. These can also lead to infections. Swelling of the legs and fluid retention, tearing of the eyes, and numbness in the fingers and toes. But even though there is a higher rate of side effects with docetaxel-based treatment, the quality of life still seems to be better in those patients who receive docetaxel when that's compared to mitoxantrone or prednisone.

JAMES A. EASTHAM, MD: Medical oncologists are very experienced with dealing with these toxicities, if you will. And as long as the patient is monitored, the treatments can be adjusted appropriately. And in general, the medications are very well tolerated.

ANNOUNCER: When men with advanced prostate cancer begin to fail on hormonal therapy, their disease has entered a very serious stage. That's why data showing chemotherapy can extend their lives is so important. Beyond the direct benefit to patients, the results from the trials with taxanes show researchers they are on the right track.

JAMES A. EASTHAM, MD: We had never shown a survival advantage for any type of drug, chemotherapy or not, in this stage of disease. So while it's certainly not a home run — we're not curing all of these patients by any means — it gives researchers and clinicians and most importantly patients, some hope that we've started to open a door that previously in prostate cancer hasn't led anywhere.

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