The big advantage of the combined therapy is that it seems to stretch out the time that hormones work—the time to progression of cancer is lengthened by several months. However, overall survival is not significantly better for the men on the combined treatment. In a huge analysis of about five thousand prostate cancer patients in Europe and America, doctors studied overall survival and found, at five years after treatment, a 3 percent difference between the men on total androgen blockade and the men who underwent castration or took LHRH agonists alone. This is not a stunning display of the success of total androgen blockade.
And, after a certain point, some patients actually benefit from stopping flutamide. For example, when a man taking flutamide in combined therapy begins to relapse—when his prostate cancer begins growing again, and his PSA level goes up—one step his doctors should take right away is to stop the flutamide. In from 40 to 75 percent of these men, PSA levels drop when flutamide is stopped. Paradoxically, flu amide can make some patients—who initially were helped by it—worse. Exactly why this happens is not clear. In certain prostate cancers, over time, the androgen receptors (the part of the cell responsive to hormones) undergo a mutation—and all of a sudden, flutamide stimulates the cancer. Remember, flu amide normally acts like a dummy key in the “lock” (the receptor), whose purpose is to block testosterone and DHT from activating the receptor. With this mutation, however, the flutamide key actually works—it turns in the lock and activates the receptor.
There is one crucial concept here that you need to understand: Ultimately, total androgen blockade is going to stop working, just as every other kind of hormone therapy does. Anyone who leads you to believe otherwise is not doing you a favor. And when hormone treatment stops working, it’s not because of the tiny amounts of testosterone and DHT being made by the adrenal androgens—in other words, it’s not the fault of some renegade hormones that are sneaking through the hormonal blockade. It’s because of the hormonally independent portion of the cancer—the cells that couldn’t care less what hormones its host is taking, because hormones have no effect on this portion of the tumor. Using hormones to fight these cells is like trying to kill a cockroach with hair spray instead of insecticide. The problem is, we haven’t found the right “Raid” yet.
As one Johns Hopkins molecular biologist explains, “Cancer cells are very efficient. And as they keep dividing, they jettison some dead weight. One of the first pieces of unnecessary baggage to go may be the system of controls—the part of the cell that takes orders from hormones. Over time, the deadliest cancer cells survive because they become pure, stripped-down growing machines.”
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