There are different methods of performing ADT; these methods include continuous or intermittent as well as differences in the actual blockade itself. Understanding the superior schedule as well as the superior combination of drugs can both delay the onset to castrate resistance as well as provide for a longer overall survival (OS).
In a research study Combined Androgen Therapy (CAB) with more then one drug having different modes of action was compared to Monotherapy where only one drug was used for the ADT. The researchers defined the time to the on set of Castrate Resistant Prostate Cancer (CRPC) as PSA progression or other disease progression. They stratified the men into three risk groups using JCAPRA score (JCO 2009; 26: 4309). In addition to the time to CRPC, overall survival length (OS) after initiating ADT was analyzed.
They found that the time to CRPC was significantly longer in the CAB group than in the monotherapy group in both the intermediate and high risk groups. They also found that in the intermediate and high risk groups OS was significantly longer for the men with CAB.
Monotherapy can be attractive because it inherently will cause less side effects, however for men with intermediate and high risk prostate cancer that is still hormonally responsive CAB should be considered superior. Men on CAB had a longer duration to developing CRPC as well as a longer OS.
J Clin Oncol 30, 2012 (suppl; abstr e15106): Hideyuki Akaza, Shiro Hinotsu, Japan Prostate Cancer Study Group (J-CaP); Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan; Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan
Joel T Nowak, M.A., M.S.W.
How would I find out more about what kind of CAB would be appropriate? Neither my local urologist or oncologist at MD Anderson has mentioned this to me and I would rather take charge than leave it to them.
Mike – CAB is combining a drug that will prevent (actually slow down) the production of testosterone as well as one that blocks any testosterone that is produced from accessing the androgen receptors and making its way to the cell nucleus. Drugs that fit the first criteria (not all) include Lupron, Zoladex and Degarelix. In the second category would be Casodex. Some men will also add a 5ar-inhibitor (proscar or avodart), but this drug is controversial. – Joel
A newbie here I asked earlier about combining Xtandi with Lupron as a CAB. Would Xtandi be substitute for Casodex in this CAB approach? Is it necessary to give eh secondary drug at the same dosage as if mono therapy? I read a post on another site where the CAB used was Lupron-Casodex-Proscar. The just prosper for 5 years before it started to fail as a mono therapy. Hmmm. With the superior result you mentioned by CAB shouldn’t those of us in the higher risk group be on that plan from the start? dWould I be out in left field by using a CAB of Lupron-Ztandi-. Of Lupron-Xtandi-?. I already was thinking to know it down hard early, but needing guidance.
Thanks
Rick
Rick, For a Newbie you have asked some excellent questions. Actually, these all are questions being asked by the researchers and clinicians in the prostate cancer world. At this time these are questions without any evidenced based answers.
Until these alternative combinations are evaluated in a clinical trial we can only guess at the answers. Guessing can be a dangerous game as I have seen that what appears to be logical doesn’t always work. As a matter of fact, it is possible that the logical combinations could end up hurting a man. For example I could suggest (don’t misunderstand me as I do not mean to suggest that this is the case) that starting CAB with Lupron and Xtandi will shorten the efficacy time of the treatment as opposed to the current standard of care, Lupron and Casodex.
The other issue you would face if you wanted to go “Off Label” is the insurance issue. Many insurance companies will not pay for experimental or “off label” treatment. The cost of the newer drugs (Zytiga and Xtandi) is many thousands of times more expensive than Casodex.
In response to your question about dosage size for mono-therapy vs. CAB for Casodex all I can really say is that in the United States the current FDA approved standard of care is combining Casodex with Lupron (or similar drug) at a 50 mg. per day dosage as opposed to the common practice in the UK of using Casodex mono-therapy of 150 mg./day. This is not to say that there are not men in the U.S. who do use Casodex mono-therapy as their treatment. I am aware of a number of men and they play with their dosage changing it between 50 mg/ every other day to 150 mg/day. – Joel