(Hormonal therapy is a frequent subject in QUEST. Please see Quest, Fall 2007, Hormonal Therapy Explained.)
1. Q: What are the differences between intermittent and continuous hormonal therapy? And would you recommend one over the other?
A: A downside of hormone therapy for men with prostate cancer is that with continuous therapy you dont feel normal because of hot flashes, loss of muscle mass, losing calcium from the bone, dryness of the skin and sometimes loss of energy or mental alertness.
The advantage of the intermittent therapy is that the patient takes the hormonal therapy until the PSA goes to zero and then stops until it drifts back to 4 and then goes back on it until the PSA goes to zero again.
With the intermittent therapy, men are only on hormonal therapy about half the time of those on continuous treatment.
The important question to answer is: Is intermittent therapy as effective as continuous hormonal therapy? And now some studies are showing that the men on intermittent hormonal therapy actually do better than men on continuous therapy.
I think intermittent therapy is a good choice for most men and does spare some of the side effects of the continuous therapy. Some men can stay off therapy for two or three years before they have to start again.
2. Q: Do you recommend hormonal therapy in conjunction with radiotherapy?
A: Studies seem to show that hormonal therapy added to radiotherapy is beneficial in high risk (locally advanced or high Gleason grade) tumors treated primarily with radiotherapy. Since there is little downside risk to hormonal therapy, I usually recommend that my patients take hormonal therapy one month before and a few months after radiotherapy.
3. Q: How long will Lupron and Casodex work and what comes after they dont?
A: The answer to how long they will work is unknown. At the present, no one can predict the duration of response to hormonal therapy.
I usually tell men starting hormonal therapy about my most successful patient who at the time he was diagnosed had cancer spread to his bones and all over his body, and he was not a candidate for surgery or radiation.
He was placed on hormonal therapy and his PSA remained undetectable for 19 years.
Some men will stay in a remission for long periods of time 10, 12, or 15 years and there are other patients for whom the time will be much shorter. The remission time is completely unpredictable in individual patients.
If the PSA rises while on Lupron and Casodex, other types of hormones are available and a more effective form of chemotherapy is also available.
In the pipeline are new experimental treatments involving immunotherapy, gene therapy. They are not ready for prime-time now, but in three to four years from now may offer better and more effective treatments with less side effects than treatments we have now.
Eventually, genetic studies will show us which tumors are going to be responsive to hormonal therapy for a long time and which are destined not to respond as well.
4. Q: How do you treat for prevention of bone loss as a result of hormone treatment?
A: My practice is to order bone density tests annually on patients who are on continuous hormonal therapy or by virtue of removal of the testicles.
If the bone density is significantly reduced, I advise vitamin D and calcium supplements and consider using bisphosphonates. In addition with established bone metastases, clinical evidence suggests that bisphosphonates might reduce significant skeletal problems.
5. Q: Please tell us about Plenaxis?
A: You should check the Internet for a more detailed description, but, briefly, plenaxis is an injectable drug that is similar to Lupron or Zoladex,
except that it does not cause an increase in testosterone levels ("flare response") before lowering them.
Thus, it is possible to give it without using an antiandrogen, such as Casodex or Flutamide to block the testosterone "flare" response that occurs during the first 10 days or so after an injection.
It probably would have been a significant improvement over the drugs currently used; however, the disadvantage is that relatively large quantities of the drug have to be injected, and some patients have had a severe allergic reaction to it.
The FDA has approved its use when other drugs cannot be used.
6. Q: What is the difference between Zoladex and Lupron? Which is the most effective? Which has the least side effects? Which do you recommend?
A: They are comparable and equally effective, in my opinion.
Lupron is given with an intramuscular injection and Zoladex is given with a subcutaneous injection that requires local anesthesia, because the needle is large.
7. Q: My urologist would like me to begin hormone injection therapy while I wait to have my radical prostatectomy. What are you thoughts about the injection therapy prior to surgery?
A: Preoperative hormonal therapy can cause scarring around the prostate that can make it more difficult to perform nerve-sparing surgery.
8. Q: How quickly does Zoladex (the 3 month shot) take effect?
A: Usually within a month.
9. Q: My husband is 57 and was diagnosed with bone metastases from prostate cancer. He is getting hormonal implants every 3 months. What sort of questions should he be asking his doctor and what is the prognosis?
A: He should ask about the trend (the rise in his PSA level over time) in his PSA level. He should also request that his bone density be monitored. He should ask about receiving treatment for his bone density, since he has established metastases. The prognosis is uncertain in an individual patient. Some patients can remain in remission for long periods of time. (See the QUEST article, Hormonal Therapy Explained)
10. Q: If hormone therapy can’t cure prostate cancer, what is it doing?
A: Hormonal therapy causes most prostate cancer cells to undergo genetically programmed cell death (commit suicide) but never all of them. Some prostate cancer cells are resistant or can adapt to hormonal therapy and continue to survive.
I recommend a PSA test every 6 months and a digital rectal examination once a year. If the PSA is in the undetectable range and the digital rectal examination reveals no lumps or bumps that seem suspicious for recurrent prostate cancer, no further testing is indicated.
Although the vast majority of patients with recurrence of their cancer have a rising PSA, a few have a high-grade cancer that might not produce much PSA but might be detected on a digital rectal examination.
11. Q: After two years, Lupron shots are no longer effective. I’ve already had radiation therapy. What does it mean when the Lupron is no longer working and what happens next?
A: This situation is explained in my QUEST article, “Hormonal Therapy Explained” (See my website, www.drcatalona.com). Secondary hormonal therapy with Casodex, Nilandron, or Eulexin is usually effective for a time.
If these do not work, ketoconazole plus hydrocortisone is usually effective.
In addition there is a new drug called abiraterone that is not yet approved that appears to be effective in early clinical trials. Other hormonal therapy drugs (MDV3100) are being developed in the pipeline.
Finally, docetaxel plus prednisone has been shown to be an effective form of chemotherapy.
A medical oncologist usually administers these treatments.
12. Q: My husband has been advised to start radiation and hormone therapy. One doctor says to start both now. Another says he should have hormone therapy for a while before starting radiation. What do you recommend and why?
A: In patients with "high-risk" prostate cancer (higher Gleason grades, tumor volumes, or PSA levels), studies show that hormone therapy given before, during, and after radiotherapy improves the results.
It is believed that the hormone therapy kills many of the prostate cancer cells and also may make the remaining cells more vulnerable to the damaging effects of radiation.
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