Zytiga vs. Xtandi vs. Radium 223 vs. Cannabis

Dx 9/2010 with agressive PCa. Failed RP, hormone injections every 3 months. Mets in pubic rami. Current diagnosis 1mCRPCa. On Trelstar, Xgeva and Zytiga. Recent blood labs showed rising PSA. Next blood lab late July. If PSA continues to rise: New nuclear scans and an eye toward replacing my Zytiga therapy with Xtandi. As you can see from the following abstract, the differences are nominal. I've been on Zytiga for 13 months.

How Effective is Xtandi vs Zytiga?

The effectiveness and safety of Xtandi were demonstrated in a clinical trial that included 1,199 men who were given either Xtandi or placebo. Median overall survival among men who took Xtandi was 18.4 months compared with the placebo group at 13.6 months. Thus Xtandi extended survival by a median of 4.8 months.

Zytiga was evaluated in a clinical trial with nearly as many participants (1,195 patients) who received either Zytiga once daily plus prednisone twice daily or a placebo. Median overall survival for men who took Zytiga was 14.8 months compared with 10.9 months in the placebo group. This resulted in a median extended survival of 3.9 months.

My question for the group is, has anyone followed the same therapy sequence as me? What were your experiences? Has anyone advanced from either of these therapies to Doxetaxel (drip infusion chemotherapy) or radium-223 (Xofigo) therapy? If so, what have been your experiences? Lastly, has anyone skipped any of these therapies in favor of a canabis based therapy?

Any thoughts/comments?

Peace. Greg

17 Replies

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  • Hi Greg,

    Xtandi & Zytiga act in quite different ways. Xtandi is an antiandrogen that operates directly on the androgen receptor [AR], whereas Zytiga stops the conversion of pregnenolone and progesterone to androgens.

    However, common to both is a potential reason for drug resistance: the emergence of Androgen receptor splice variant 7 [AR-V7]. This means that when one drug is taken after the other has failed, there is an increased chance that the second will be ineffective.

    {I don't know if both have been tried together. (I have heard of Zytiga + Casodex, another antiandrogen).}

    -Patrick

  • Patrick you are spot on about the AR mutations (i.e. AR-V7). It's been implicated in both abiraterone and enzalutimide resistance. Greg, I think before you move to next step you should consider getting genomic sequencing. There's AR signaling pathway alterations that would be useful to find out about and you may have a completely different driver mutations for your cancer (i.e. pi3k pathways, Wnt pathway, cell-cycle pathway, dna repair pathway) that would be better served on a trial or on emerging drugs / off label use, etc. Trials aren't for everybody, you likely have to travel but it's a good way to see different part of the country and the drug companies/PI reimburse for most of the costs. You're probably thinking, "WTF is this guy talking about? My doctor didn't mention any of this!" Exactly. It's not standard of care. My 2 cents.

  • Hey Bryce, thanks for the post. There is no such thing as WTF in this crazy war we're waging. See my responce to Patrick's post. The info you shared is interesting...and I knew/know nothing about genomic sequencing, other than I've heard the term before. A little help...what is the best way to approach genomic sequencing and does private insurance ( I have it till July 1, then medicare) or medicare cover it? Your 2 cents might be worth a lot more, Bryce! Thanks again!

  • Thanks for the post, Patrick. I didn't mean to minimize the differences between the two. It was really a frustration comment about the Survival rate on each being so similar. I know that different med sequencing often has no common outcomes, each of our cancers being their own little unique event. I'm trying to get a little bit more educated about options and (anecdotal) information from others. Metaphorically, I'm looking at the fact that I've used a number of bullets in this gun fight with cancer...I'm wondering how many bullets I have left before the chamber is empty... and which shot should I take next.

  • I think I have been through it all!

    Zytiga worked for nine months with no side effects.

    Xtandi was a disaster for me. Huge side effects and not much results.

    Xofigo was good for pain.

    Doxetaxel effective for a short while.

    Provenge absolute waste of time and money.

    Jevtana last resort at this time.

    Cannabis: Very effective for sleeping (25% THC) especially when going through kemo.

    That's my story!

    -Mike

  • I'm also very curious if anybody on this forum has seen their mCRPC mets melt away with cannabis. There's a lot of advocates for this on Facebook / other forums. But does it really work? Really? If so, what's the ideal ratio of CBDs/THC? I have a friend with breast cancer who swears by CBDs but she's also jacking her system up with countless other naturopathic things so who knows what is really working/contributing. Furthermore she doesn't have mets on bones or organs, just lymph node...so I want to read about a mCRPC guy who had wild success with cannabis if any exist.

    Greg, sorry but I can't give you any advice on the pros/cons of the other things you asked since I haven't tried them, I just think sequencing would be wise per my other note.

  • I hav been through Zytiga, which worked for the better part of a year, then Xtandi which not worked for a few months. Next came docetaxel, which worked from May 2015 until April 2016 (including a 3 month break). Started on cabazitaxel 3 weeks ago (having second infusion on Monday). The good news is that I had no side effects with any of the treatments. If the cabazitaxel isn't effective my oncologist is recommending a clinical trial. Good luck with your treatments.

  • Thanks for your post. I was unfamiliar with cabazitaxel so I googled it. It appears that it is in phase II of clinical trials at Memorial Sloan Kettering. Are you part of this trial? May I ask what state you live in? Thanks.

  • Cabazitaxel (Jetvana) is the standard of care drug after docetaxel. No trial yet (and probably not for a couple of months unless something goes south. We live in Washington (Seattle) and have a second home in North Carolina. In Washington my doc is at Univ. Washington. In NC I go to Duke.

  • While Sloan may be doing a trial with cabazitaxel (Jetvana) it's been used for quite a while. I live in Seattle, and receive treatment mostly at University of Washington, but I am also a patient at Duke in North Carolina.

  • i tried cannabis but it made me feel less than well. i live in Colorado where you get a tax break on cannabis if you have a prescription from a Dr , so i went to see a Dr that would prescribe, thinking i would be paying $80.00 for a piece of paper. instead he told me i should have started out with a micro dose and worked my way up. also with my age (87), COPD,pacemaker,etc. he felt i would die of a heart attack or other things before prostate cancer and cannabis might contribute to my loosing balance contributing to a fall, etc. i chose to leave without a prescription and he charged me $0.00 which surprised me . bear in mind these are my unique circumstances.

  • Thanks for the post!

  • Greg & Bryce, I'll do a separate post, probably tomorrow, to share some info on medical cannabis.

  • Hi Greg,

    Here is my experience with Zytiga and Xtandi I had started with Zytiga + prednisone, full dose, which brought my PSA down from 136 to about 50 after just 2 months. But it was also an energy wipeout, and sent my liver function tests through the roof. I went off it for two months to allow my liver to recover, then restarted it at half dose, but the liver enzymes started to rise again, so I stopped it. I started on Xtandi, but only took it for 10 days, because I wanted to see if I could reduce my fatigue and get some energy back, getting some but limited improvement. But during the time I was not an either med, the PSA continued down, with a nadir of 11. It stayed this low for a couple of months then gradually began to rise, and I resumed the Xtandi. The PSA did get as low as 12, but then began a slow rise to where, after 19 months, it is now at 89. No liver problems, but a gradual increase in fatigue. A recent scan has shown some lung metastases, in addition to the ones in the bones, so I will be changing my treatment regimen. Comparing my response to others in this post, clearly it is an individual, and basically unpredictable matter.

    Incidentally, re Xgeva, I was on it for 18 months, and about 8 years ago, had concluded being on Fosamax for 7 and 1/2 years, for osteopenia. A lower left molar tooth became troublesome, becoming loose and painful on bite, and had to be pulled. This led to a diagnosis of osteonecrosis of the jaw (ONJ). Returning to Xgeva appears highly doubtful, but no one can say for certain how much risk might be involved. A cautionary tale.

    Good luck,

    Les

  • Thanks for the reply! I've been on Xgeva for about 2 years with no apparent side effects. I'm just struggling with "next steps". I'll be losing private insurance on July 1, going on medicare. I don't know how they'll look at me from a meds point of view. My fatigue (it's now 4:20 am - been awake for over an hour) is due in large part to my ADT regimen, Trelstar. Just had a shot of Tresltar and Xgeva this past Thursday. It often seems that I'm pretty much wiped out for a few days after the shot. Again, thanks for your input, Les.

  • I made the switch to zmwdicare with a private supplemental insurance ( not just drugs) last year. Things administered at the hospital (all infusions) fully covered by Medicare. Other prescriptions subject to individual insurance. You will need to check what you take against theirvapproved schedules.

  • Diagnosed last year,PSA 2700, innumerable bone and lymph node mets. Lupron and Docetaxel right away. Lupron decreased PSA to nadir of 12, but increased during chemo. Started Xtandi and Provenge in January, PSA 32, but PSA continued to rise. Started Xgeva and Zytiga/prednisone last week with PSA at 160. Pain in lumbar spine much better. MRI last week showed crush fx L1-3. Tolerating Zytiga much better then Xtandi. Pain and emotional lability improved. Age 45. Will report if PSA declines at all. Onc is hopeful but cross resistance is of course a concern.

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