Trials start for new form of androgen deprivation therapy

Volunteers are now receiving doses of GTx’s luteinizing hormone (LH) inhibitor — GTx-758 — in a Phase I clinical trial.

GTx-758 is (as far as The “New” Prostate Cancer InfoLink is aware) the first direct LH inhibitor to enter clinical trials in the U.S. According to GTx, GTx-758 would differ from available forms of androgen deprivation because it would be taken orally, not injected.

Preclinical in vitro and in vivo data suggest that GTx-758 can rapidly suppress the secretion of LH, thereby inhibiting production of androgens by the testes. GTx believes GTx-758 has the potential to reduce testosterone, a primary growth factor of prostate cancer, without also causing certain side effects such as bone loss and hot flashes which are common with current androgen deprivation therapies (ADT) for prostate cancer.

4 Responses

  1. WOW! This could be big…. My husband has been battling prostate cancer for some time, and has been on hormones for 3 years. No one thought to check osteoporosis because it was “intermittent” hormone therapy…. He has 4 broken vertebrae and osteoporosis in the spine and osteopenia in the hips.

  2. My husband has been treated for prostate cancer for several years now and is currently being treated with hormone therapy (Lupron) He has osteporosis, as a side effect of Lupron. (We were told it shouldn’t have been an issue until it was “continual.” He was treated “intermittently.”) … He currently has four broken vertebrae in his back (upper) and lower back has osteoporosis, osteopenia in the upper hip area.

    This could be avoided! But, men should be treated with something to protect bones as soon as they go on hormones.

  3. That would be quite an achievement if it works as they seem to hope it will, but I’m a little confused: Are bone loss and hot flashes caused by the Lupron itself or by its success in suppressing the production of testosterone? I’ve always believed it was the lack of testosterone circulating in the person’s system. Was I wrong on that?

  4. Dear John: Much as I would like to be able to tell you that we know exactly how the use of LHRH agonists like Lupron lead to bone deterioration and fractures, I don’t believe that we do really, really know.

    Now in normal men and women, bone is constantly being rebuilt and destroyed in a process of bone cell turnover. (Don’t think that your bones just grow when you are a child and stay like that until you die!) A type of cell called an osteoclast is important in the routine process of bone breakdown and removal. However, in certain categories of bone disease the osteoclasts become overly active, and the normal balance between the activity of osteoclasts and their bone-building counterparts, the osteoblasts, is knocked out of kilter. As a result, bones begin to deteriorate because there is more bone breakdown than bone building going on. When osteoclasts encounter bone, they attach themselves to it, and when the link takes place, microfilaments help to transport an enzyme called V-ATPase from the core of the osteoclast to its surface. Once there, the enzyme activates effects that cause the bone to degrade.

    The question, then, is exactly what causes this increased activity of the osteoclasts compared to osteoblasts. It is certainly not the Lupron directly, but whether it is a lower testosterone level or some other hormonal effect of the “shutting down” of the hypothalmic- pituitary-adrenal axis, I do not know. There is a video on line that (partially) attempts to explain how a drug like zoledronate (Zometa) can slow down or stop the process of bone resorption, but even that video admits that the manufacturers of zoledronate don’t know exactly how it works.

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