William R. Berry, MD
Imaging agents for patients with prostate cancer continue to receive FDA approvals, according to William R. Berry, MD. For example, carbon-11 acetate PET/CT scans, 18F-sodium fluoride PET scans, and fluciclovine have been recently approved to add further imaging options for patients.
on Genitourinary Cancers, Berry, a medical oncologist at Duke Cancer Institute, discussed luteinizing hormone-releasing hormone (LHRH) agonists versus antagonists as treatment options for patients and highlights the novel techniques for prostate cancer imaging.
OncLive: Can you please provide an overview of your presentation?
: My presentation was on 2 different topics related to prostate cancer. The first was the difference between the therapies of LHRH agonists versus antagonists, particularly with an emphasis on safety issues that may be related to the choice of agent.
The second part of the talk was related to new imaging techniques in prostate cancer and how they might enable us to localize disease more effectively.
What are the differences between agonists and antagonists?
LHRH agonists and antagonists are similar drugs in the sense that they have the same clinical indication. They indicate for the decrease of testosterone production by the testicles. They work through the pituitary gland but they do have some differences in how they do that.
The agonists, which have been around since 1980, include leuprolide and goserelin, among others. There are 5 or 6 different FDA-approved drugs that fit that agonist category. They are called agonists because, when they bind to the LHRH receptor in the pituitary, they cause an initial stimulation of the receptor, which results in an excess release of LH and follicle-stimulating hormone (FSH). This causes testosterone to release early in the testicles within the first 10 days after therapy.
After that initial surge of testosterone is released, there is a gradual tiring of the receptor and the testosterone levels go down due to the decreased secretion of the LH and FSH from the pituitary. After a month or so after the first treatment, testosterone levels will be low despite that initial surge.
There is 1 antagonist drug approved in the United States called degarelix (Firmagon). The antagonist drug blocks the receptor and causes an immediate decrease in FSH and OH secretion, which results in an immediate decrease in testosterone production by the testicles. The levels of testosterone drop more quickly without that initial surge in testosterone. That is the basic physiologic difference in the mechanism of action.
What characteristics might a patient have that determines whether they should receive an agonist or antagonist?
Before we had the antagonist, there was always a concern for people who presented with metastatic disease—particularly metastatic disease in the bone that they would cause a surge or exasperation of bone pain during that first or second week after starting therapy. The practice during that time was to prescribe bicalutamide or another antiandrogen drug to hit the tumor directly and prevent any flare of the testosterone that causes the increase in pain.
If you are concerned about symptoms arising during the first 2-week period, there may be an indication to use the pure antagonist during that time since you don’t have to worry about the issue, whereas with the agonist you might [have that issue].
You also discussed novel techniques in the field. Is there anything coming down the pipeline that you are excited about?
For years, we have had primitive imaging with prostate cancer, which included technetium bone scans that have been around for more than 50 years. For example, we have CAT scans, which have been around since 1980. It is not a bad scan but it is not very sensitive at picking up metastatic disease. CAT scans can diagnose in large lymph nodes, but they can’t tell you what is in them. We do have some new scans based on molecular imaging, such as the newer PET scans. These are small molecule photon emitters of radionuclides onto a certain type of chemical product that may be specifically taken up by the tumor.
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