Investigator Perspectives on Emerging Concepts in the Management of Genitourinary CancersTolerability of second-generation endocrine agents in prostate cancer
2:29 minutes.
TRANSCRIPTION:
DR LOVE: What problems, if any, have you seen with abiraterone? And anything specifically related to the corticosteroids? DR PETRYLAK: I think that the corticosteroid dose is small. So I’ve not really seen any major effects with the steroids. I think the major problem with the steroids is, once you’re on them, it’s hard to get the patient off of them. They do have trouble with fatigue after that. So I haven’t seen really anything from that standpoint from the steroids, major. Abiraterone, LFT abnormalities, fatigue, edema, those are the major things that I’ve seen as toxicities. DR LOVE: How about enzalutamide? You mentioned the fatigue. Do you think this is some kind of central nervous system thing? DR PETRYLAK: We do know that enzalutamide does cross the blood-brain barrier. And the question is whether some of these newer-generation antiandrogens have the same effect. We do know that there is an increased seizure rate with enzalutamide, particularly in those patients who’ve had prior chemotherapy. So yes, I do believe it’s a CNS effect that’s going on. DR LOVE: What else have you seen with enzalutamide? DR PETRYLAK: There’s an increased risk of falls. And whether that’s central or whether that’s related to sarcopenia and a little bit of muscle weakness is not really clear, but there does seem to be an increased fall risk with enzalutamide. DR LOVE: How do you decide which one to start first? DR PETRYLAK: Clearly, I like avoiding steroids, if I can. So enzalutamide is one choice in that situation. But if I get the perception that a patient is frail, fatigued and did not necessarily tolerate their primary hormone therapy well, I tend to go with abiraterone over enzalutamide. DR LOVE: What about the combination of the two? I know that’s been looked at a little bit. DR PETRYLAK: So there’s a randomized trial that’s being done in the Alliance looking at enzalutamide versus abi and enzalutamide. It makes sense to combine the two together, because they do work by different mechanisms. As we know, abi reduces testosterone synthesis and enzalutamide binds to the receptor. So one of the mechanisms of resistance to enzalutamide, in addition to AR-V7, is upregulation of testosterone synthesis. That’s been shown by the MD Anderson group, where Chris Logothetis did bone marrow biopsies and looked at testosterone levels and found that they went up after enzalutamide. So it does make sense to combine the two. Whether you’re going to see a greater effect in combination versus sequentially is not clear. |