Introduction and Current ADT Challenges

[Music] hi this is e david crawford from the university of colorado thank you for joining me and our faculty in this program entitled navigating the adverse effects of adt improving patient outcomes I bring you greetings from Colorado my disclosures are on this slide I am happy to introduce our faculty we have an outstanding faculty including dr. Thomas C King from Medical College of South Carolina Neal the Shore from the Carolina urological Research Center and Johanna --then H pictus who is from McMaster University and Ontario Canada there's a lot of history in androgen deprivation therapy going back to the 1800s with castration the first tumor marker in oncology was 1938 acid phosphatase a Nobel Prize in 1944 Huggins estrogens came along nonsteroidal and steroidal anti androgens we had LHRH agonists come along and Andrew Shelley got a Nobel Prize for that and then in the last decade we've seen a lot of new drugs introduced including the antagonists ever Alex and now Becker Alex and androgen biosynthesis inhibitors I'd rat around and really third-generation anti androgens enzalutamide the side effects of a DTS can be sort of broadly categorized under castration syndrome loss of libido fatigue hot flashes intellectual capacity changes emotional changes depression muscular strength different fat opposition's osteoporosis and cardiovascular disease we can also look at them and sort of side effects of conditions like sarcopenia bone loss leading to cardiovascular events osteoporosis and then further complications including cardiovascular death and fractures and also skeletal related events what do the guidelines say I chose the European guidelines to look at here and there is some help but not really a lot you can look here to see watch libido not a lot you can do too erectile dysfunction hot flashes we've been doing that with that for centuries gynecomastia a lot of it has to do with health healthy diet exercise things like that to deal with that we'll discuss some of those during this program one of the questions that they want to ask are all forms of ADT the same and I would say not the objects of our many decreased testosterone control prostate cancer reduced cardiovascular events urinary complications and musculoskeletal complications there's no question that cardiovascular complications are a major issue and one that we will deal with in this symposium to look at cardiovascular events it's the second most common cause of death in men with prostate cancer and this has been shown and the number of different trials this is not new we go back to 1967 and the VA studies and there was a study with men with radical prostatectomy and worki ectomy with or without estrogens clearly you can see here that there is almost a double the rate of cardiovascular events including fatal cardiovascular events and men who are on estrogens there have been a large number of observational studies that have looked at cardiovascular events including sudden cardiac death and there is a variation among these events depending on the type of androgen deprivation therapy that is utilized the FDA in 2010 issued a warning asking manufacturers of GnRH agonists to add the safety information to the drug labels about the increased risk of diabetes and certain cardiovascular diseases including heart attack sudden cardiac death stroke and men with prostate cancer if we look at antagonists vs. agonist and studies that have been done in that last decade what we see is there is an apparent difference and a number of these side effects including cardiovascular if you look at one study that was done that we will go over see us 37 with Becker Alex it showed a difference and in death rate between an antagonist and a magnet agonist another that most of the deaths early on we're related to cardiovascular not prostate cancer unary symptoms we know without after the men with prostate cancer have moderate to severe urinary symptoms there is a difference and we'll discuss those on how we treat these men with ADT and we do know that there are studies that have been done comparing antagonists to Agnes and looking at things like IPSS score and volume reduction and things like that and we do know that there is and again and some of the studies done with the antagonist a difference and the rates of urinary tract and events and then we also know that bone loss and musculoskeletal issues are common and then on ADT and in other word for three factors of skeletal complications develop at least one fracture within the first 10 to 12 years and there is a higher mortality associated with that we look at these musculoskeletal events again there's some discrimination and difference between the type of ADT use so in conclusion ADT therapy is associated with many side effects and the most prominent one and when you're concerned about a cardiovascular we'll discuss all of the side effects during this program we need to monitor these and try to navigate the patient through the issues with cardiovascular and other events [Music] you