after failing multiple times on regular ADT plus SBRT and finally failing LU– 177 and Provenge, my PSA went on the rise again. I’ve been on mono Xtando for six weeks and not feeling well despite trying to exercise heavily. Going in for bloodwork tomorrow. What kind of labs should I ask for?
Anyone else on this monotherapy with side effects? Brain fog and fatigue is totally debilitating.
Side effects from Xtandi monotherapy can vary from person to person, but some common ones include fatigue, hot flashes, hypertension, nausea, diarrhea, joint pain, and headache. Additionally, some individuals may experience more serious side effects such as liver problems, seizures, or allergic reactions. It's important to discuss any concerns or symptoms with a healthcare provider to determine the best course of action.
Thanks. What should I look for in my blood work to see if it’s causing internal problems?
I think please coordinate with your MO and tell your symptoms. I usually write down in details and MO read my notes. It helps MO to order blood work and come up with actions plan.
I'm currently on mono enzalutimide. No SEs except for the usual that we all tend to experience, ie fatigue, restless legs.
Lately I've been feeling pretty good and I may attribute that to recovering T if my latest round of blood work shows an increase.
Regarding recovering T, see TA's post below. He has indicated that one gets no benefit from that T when using Enzalutamide. Are you saying differently?
It's a point that needs to be cleared up on the forum.
I'm just relaying my experience. I'm having no brain fog, very little fatigue. Whether it comports with what others are experiencing is beyond my pay grade.
So do you get any of the benefits of keeping your testosterone like muscle growth or sexual function and so forth?
Sexual function hasn't returned, muscle growth I would say is steady.The extreme fatigue and brain fog I do not have. I've been on the full 160mg for 3 months now after previously being on Eligard and 80mg Xtandi. I do feel better than before but I think I must be an outlier.
Expect gynecomastia/nipple pain (45%). Fatigue was the most common side effect and occurred more often with enzalutamide (47% for the monotherapy, 43% for the combination) than with leuprolide alone (33%).
Thanks. Dorf had me try electron radiation to my chest three weeks ago. Treatment was broken down into three sessions. Electron radiation is supposed to not penetrate deep into the muscle or bone. Wondering how successful this will be. Blood work tomorrow to see how liver is holding up. Interesting though, a week after starting Xtandi PSA dropped immediately but testosterone also dropped to castrate level. I thought that was the point of Xtandi--we get to keep our testosterone.
No, that is not the point of Xtandi monotherapy. It blocks all your T receptors on all your cells, not just cancer cells. With nowhere to go, T levels build up in the blood. After T reaches a high serum level, the pituitary shuts down your testicular production (similar, but not as complete as the T-surge caused by Lupron). Frankly, I fail to see the attraction of Xtandi monotherapy: it has higher levels of fatigue and less oncological effectiveness.
Understood. The fatigue is overwhelming and I mostly skated through Orgovyx by training hard. So what's my alternative?
Someone in my group takes Ritalin. There is an ongoing clinical trial at MD Anderson if you are interested:
classic.clinicaltrials.gov/...
What about if I switched to another second generation med? Which one has less side effects?
There has never been a randomized comparison, so there is no data to go by. One of the most prevalent adverse effects of ADT is fatigue, so IDK how much it can help changing the 2nd gen medicine. Darolutamide is said not to activate GABAA receptors that promote sleepiness, but fatigue is still a prevalent side effect.
I just got my PSA test back and although it’s not quite nondetectable, it has been reduced substantially from the enzalutamide. Dr. Kishan at UCLA recommends SBRT to the four new small spots the last PSMA scan showed.
So far the enzalutamide side effects of fatigue and appetite suppression from the afternoon on are intense. Normally I lift heavy three times per week but because of endoscopic spine surgery a month ago have not been able to return to wrestling until this coming week. That makes a significant difference. I’ve heard pros and cons regarding SBRT and this would be my fourth attempt with it in the last four years. What do you think the downside is? Also did Provenge treatment six months ago so maybe that’s still strong enough in my system to help with the synergetic effect?
No one knows if SBRT to spots accomplishes anything oncologically (it will relieve pain from painful mets). Your cancer is systemic, so there will always be new spots. So far, there have only been small Phase II trials and the benefit has been limited, if any. But, until we have better data, my attitude is, if safe, why not?
Now, safety may be particularly a concern when metastases are in the chest area or near the esophagus or bowels. Sometimes spinal metastases have penetrated soft tissue and special care must be taken. But I know Dr.Kishan is very careful, and he would never recommend SBRT where it is dangerous.
Sometimes SBRT will cause painful inflammation that can be relieved with NSAIDs or Medrol dose pack.
So what kills micro mets before they grow into tumors. I thought that was the purpose of the LU-177 in the Eclipse trial. But although PSA dropped to .25 before shot number four, directly after PSA shot back up. From what I'm reading, no one has had a drable remission from Lu-177 yet, only temporary drops in PSA.
I realize being systemic means no cure--what's the best option for durable remission?
Sadly, nothing we have kills them all, and the resistant ones will eventually replicate and grow into tumors. For example, Pluvicto only kills those that express PSMA, ARSi only kill those that are still sensitive, docetaxel only kills those that are actively growing, PARP inhibitors only kill those with BRCA+, Xofigo only kills bone metastases that are growing.
Thanks TA. Dorf said I could qualify for this trial at COH. Ac225-hk2
Liggands might work on prostate cancer other than PSMA avid. I'm cautious because of Actinium's permanent damage to saliva glands and tear ducts. Actinium is described as 500 times more powerful than LU-177. Easier on the kidneys though? What do you think?
hk2 is a kallikrein, similar to PSA. so almost all prostate cancer cells may be vulnerable, even more than PSMA. It is the PSMA ligand that attaches to salivary glands and tear ducts, so the hk2 ligand would NOT attach there.
If it is excreted through the kidneys, there may be some kidneys toxicity, but IDK if it is, or how rapidly it is.
I think it's a great trial!
I'll be speaking to Dorf this week and pass on info here.
Fatigue and brain fog are common, also headaches, joint/muscle pain and BP issues. Some guys do well on lower than SOC dosage. I’ve been taking Xtandi for nearly nine years now, about four years ago SE’s got to be too much (they seemed to be cumulative) so my MO, Dr. Sartor reduced the dose so now I’m on a half dose- 80mg and it’s working and SE’s are better, not gone but better. Some docs will prescribe Ritalin for fatigue and brain fog and Celebrex for headaches and joint pain. 😉
Ed
I take Xtandi, Lupron and Avodart, yes I became castrate resistant about two years ago. I was dx stage 4 over 10 years ago, somehow Snuffy Myers was able to prescribe Xtandi back then without me being resistant at the time, back then you had to be resistant to be prescribed Xtandi.
Ec
So if I’m still feeling crappy after the upcoming SBRT treatment maybe I’ll try that idea of reducing the enzalutamide from 160 down to 80. Liver panels came back OK but there’s no telling how long those remains stable.
I would not make any changes without consulting your doctor, in my case my PSA was undetectable and the SE’s from Xtandi had become intolerable, it was much more than just feeling crappy.
Ed
Thanks Ed. Wrestling twice a week is pretty hard-core exercise, especially combined with hiking and lifting weights, but really works magic on side effects. At least it did with Orgovyx. So when I get back on the mats this week, I’m hoping for the magical transformation. And probably also proceed with SBRT treatment. What did you do to maintain your hemoglobin? Mine still remains in the 10s
I take an iron supplement in the evening on a full stomach, I get my iron blood levels checked every few months to make sure I’m not overdosing.
Ed
I also take an iron pill but also have had two direct iron infusions over the last few months. The next day it’s like being super charged in my workout, but hemoglobin fades after a few days and only bumps up a half a point. I am wondering if the four LU – 177 treatments last summer permanently damaged my bone marrow.
Hi Ed ,
Just trying to understand. If one is castrate resistant , lupron and enzalutamide still work ??
To some extent yes, both may still be working on a good portion of the tumors/micro tumors that you have, however there may be some that have found a workaround to testosterone suppression (Lupron) or an androgen blocker like Enzi. So using something like targeted radiation to the resistant tumors can be beneficial. That’s where scanning comes in, to find those active tumors and treat them if possible.
That’s the way it is in my case, I radiated two ribs and PSA was reduced because those tumors were destroyed. But I’m pretty confident that I have numerous other tumors that are being kept dormant from ADT.
Ed
If you are asymptomatic, you might want to consider BAT therapy, developed at Johns Hopkins.
BAT therapy is for men who are castrate-resistant and their PSA keeps rising. It uses pervading injections of high-dose testosterone to "reset" the castrate-resistant cancer cell into being hormone-sensitive again. You continue to take Lupron (etc.) ADT during the entire process. It's a relatively new protocol (7 years) so there isn't 10 year survival data on it, though.
Xtandi side effects
Xtandi side effects
Xtandi side effects? 
XTANDI SIDE EFFECTS
Xtandi side effects
