3.26.07 Treating Prostate Cancer After Lupron Fails

Frequently men come to my clinic after having failed treatment with Lupron or similar drugs, like Eligard, Zoladex, and Trelstar. These drugs aren’t perfect and they don’t suppress testosterone in every man. The first step in treating a man who’s failed Lupron treatment is to measure their testosterone and dihydrotestosterone blood levels. You would be surprised how often we find that there’s enough of either testosterone or dihydrotestosterone to fully explain why the treatment has failed. I find it very puzzling that most urologists don’t measure testosterone in their patients and that nearly all fail to measure dihydrotestosterone. If the goal of treatment is to lower androgen levels, it seems obvious to me that you would want to measure androgen levels to make sure the drugs are working. When you go on a diet, you measure your weight. When you depress the gas pedal on your car, you look at the speedometer. So, when you are trying to treat cancer by suppressing testosterone, you check to see that the drugs are doing what they should. This is not rocket science. If Lupron doesn’t do the job, often switching to one of the competing products will get the job done. Surgical castration is another option. The final option is to prevent the remaining testosterone from binding to the androgen receptor.

In the previous section, we discussed how a prostate cancer that progresses after Lupron is still dependent on testosterone and outlined the various mechanisms the cancer cell uses to grow despite low testosterone levels. It turns out that in nearly every paper published on this subject, researchers added Casodex and subsequently showed that it prevented low levels of testosterone from supporting cancer growth. The concentrations of Casodex used are similar to those obtained in patients who received 150–250 mg of oral Casodex per day. I can find only one clinical trial that has tested this. Brown, R.S., et al biopsied the metastatic cancer masses that continued to grow despite medical or surgical castration and tested for androgen receptor content. In those patients where the cancer appeared to be making an abnormally large amount of androgen receptor, Casodex caused a response in 80% of the patients.

Since I opened my clinic—the American Institute for Diseases of the Prostate—in 2002, I’ve made it a practice to measure dihydrotestosterone levels in each patient we see. And I have to tell you that medical castration, while effective at reducing testosterone from the normal range of 300-800 ng/dL to below 30 ng/dL, often leaves dihydrotestosterone levels within the normal range (30-80 ng/dL). And dihydrotestosterone is ten times more powerful than testosterone at stimulating prostate growth, so a dihydrotestosterone of 30 ng/dL is potentially as powerful as a testosterone of 300. Dihydrotestosterone formation can be blocked in most patients with either Proscar or Avodart, with Avodart being more consistently effective. I’ve found this can aid in inducing remission in patients who’ve failed Lupron. Luckily, Proscar and Avodart don’t cause any additional side effects in men on hormonal therapy. But again, we have to measure dihydrotestosterone levels to see if Proscar or Avodart are in fact suppressing dihydrotestosterone.