Wednesday 12 December 2007

Hormone Resistant Cancer

What happens if my prostate cancer stops responding to the hormone treatment? This was the question that had begun to enter my thoughts. As a result, I decided to research this possibility and found some very useful information which I now share with you the reader.

"When prostate cancer advances to later stages, it can become resistant, or refractory, to first-line treatments.

As prostate cancer tends to advance, men will get some kind of what is called hormone therapy, androgen deprivation therapy, hormone manipulation, many different names where basically we attempt to suppress the testosterone stimulation for the prostate. Although most prostate cancers, more than 90 percent, are sensitive to this hormone change, at some point the prostate cancer for some reason that's still unclear to us, adapts.

At that point it's no longer sensitive to the suppression of the hormones or testosterone. And that's when it's called 'hormone refractory prostate cancer'.

There are many types of hormonal therapies. Even when the cancer has become resistant to some hormonal treatments, others may still be effective.

In patients that have hormone refractory prostate cancer, they continue on their hormonal therapy. Many of those patients will undergo a secondary hormonal manipulation.

In men, there are two main producers of testosterone, the testes and the adrenal glands. By late-state disease, patients have most likely had their testicles surgically removed. Another type of hormone therapy uses drugs to inhibit testosterone release by the adrenal glands.

Secondary hormone manipulations include medications, such as ketoconazole, which is an antifungal agent, but given at higher doses, it can actually suppress the hormones that are produced by the adrenal gland, so many patients can undergo a secondary manipulation, for example, with ketoconazole and steroids.

Hormone therapy at any stage of prostate cancer can affect a patient's quality of life.

Patients complain very frequently of hot flashes or hot flushes. People have different names for it and essentially it's like going through menopause for women. The second thing that can happen is they can lose bone mass and muscle, which can be very distressing to men, particularly younger men who are diagnosed with the disease. And then the last thing some patients complain that they actually don't feel as sharp. They don't think as clearly.

The survival rate for hormonal refractory prostate cancer is approximately two years. However, recent studies have shown that chemotherapy may extend the lifespan of some patients by over 20 percent.

There are two large, actually very well done studies that looked at using docetaxel; the trade name for that is Taxotere. One was a trial called TAX-327, which was an industry-sponsored trial looking at giving docetaxel plus steroid, called prednisone, and that was compared to the previously FDA-approved regimen, which was something called mitoxantrone and prednisone. And what you saw was actually about a two to three month difference in overall survival -- between those patients that got docetaxel at every three weeks compared to the previous FDA-approved chemotherapy regimen.

The second study, known as SWOG-9916, focused on docetaxel and another chemotherapy drug called estramustine.

The combination of docetaxel and the estramustine phosphate were compared to at the time the standard, which was mitoxantrone and prednisone. And again, survival benefit was shown in the chemotherapeutic arm of docetaxel and estramustine phosphate over mitoxantrone. And again, it was about a 25 percent improvement in patient survival.

Estramustine, however, may be associated with series side effects including blood disorders and abnormal clotting.

The problem with that regimen though is the estramustine phosphate does have thromboembolic and hematologic toxicities that make that not the clearest choice for patients with advanced prostate cancer.

Radiation therapy can also be used in advanced prostate cancer.

Radiation therapy is very commonly used, not only for localized therapy, but for therapy for patients who have prostate cancer that has already spread, symptomatic relief. For instance, if you have a spread of cancer to your back or to your rib or somewhere painful in your bone, it's very common to use radiation therapy. That's in a palliation sense.

Advanced prostate is an incurable disease. However, emerging therapies are helping patients live longer lives.

We now have effective chemotherapy that for the first shows survival benefit. I think that most people who treat prostate cancer believe, especially in the advanced stages, that we're not there yet with a cure for these advanced hormone refractory patients. We have probably the first piece of the puzzle with some new chemotherapy that shows survival advantage".

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