Xtandi failure

I have read the studies on the presence of AR-V7 (Onc didn't do) and regarding PSA decline by more than 50% after one month in relation to success of treatment.  PSA went from 30 to 32 over 12 weeks since starting Xtandi, post docetaxel and concurrent Provenge.  Looking for guidance on discontinuing Xtandi and moving on to Xofigo, give it more time or some other treatment.  Was castrate resistant 8 months post diagnosis and while on docetaxel and lupron.  Onc visit and lab work scheduled in 6 weeks.

16 Replies

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  • Look for clinical trials for Galeterone they will test for the AR-V7 as part of the trial (free). 

  • Though we cannot be certain if AR-V7 is present without testing, if we knew its lack of presence then Zytiga/abiraterone acetate may have a better response if you haven't had that prescribed earlier.  You mention Xofigo/alpharadin/Radium 223, but this medication is more to control pain from bone metastasis.  I would expect a next protocol would be a move to Jevtana/cabazitaxel.  Sorry to learn you are going through earlier medications without success. 

  • Hello Chuck,

    Re: Xofigo - We had a guy here in the Silicon Valley PCA Support Group report that Xofigo went beyond pain control and his bone lesions disappeared.  Time will tell how long that lasts, but Xofigo looks to be for more than pain control.  

  • True, though it isn't a medication I would rush to until MedOnc determined it was necessary because of other meds failure.  Reasoning is the side effects that could occur that can include nausea, diarrhea, vomiting and swelling of the leg, ankle or foot. The most common abnormalities detected during blood testing included low levels of red blood cells (anemia), lymphocytes (lymphocytopenia), white blood cells (leukopenia), platelets (thrombocytopenia) and infection-fighting white blood cells (neutropenia).

  • Get  tested.  I went to John Hopkins for a consultation and they tested me for ARV7.  If I recall correctly, being negative would indicate that Zytiga/prednisone or Xtandi would be effective.  I have been castrate resistant since 10/15 on Lupron after 5 years with advanced PC.  I just started Xtandi a couple of days ago.

  • Not knowing what your PSAdt was before starting the Xtandi, I would guess that the current PSAdt is higher than prior to Xtandi.  It sounds like you have a mixture of gene types, not at all unusual.  The Xtandi is working on the susceptible types and with time will eradicate them, leaving the resistant types to flourish.  I know how frustrating it is to have to wait 6 weeks.  Xtandi is very expensive medication and there is pressure to drop it sooner rather than later. 

    Best wishes

  • PSA at diagnosis one year (04/16) ago was >2700.  Absolute nadir was 12 in October.  PSA at commencement of Xtandi was 30.

  • OK, the Xtandi is definitely having an effect on the PSAdt.  The Provenge does not affect the PSAdt.  You are not getting the response you hoped for, but each man's tumor burden is different.  The fact that in three months your PSA only rose 2 gives support to the doctor continuing the treatment for another 6 weeks at least.  We're not talking cure here but control.  32 is certainly better than >2700.  And hopefully your quality of life is better on Xtandi than on docetaxil.  Attitude and exercise are oh so important, too.

  • Thank you for the replies.  Just worried about resistant strains as tumor burden increased via PET scan while receiving docetaxel even though PSA was still declining, albeit by small amounts.

  • It took time to grow to >2700 and it took time to get to 12.  You really don't want all those cancer cells disintegrating at once, as the junk would overwhelm the kidneys.

  • Interesting.   I failed Xtandi, Zitiga and Provenge.   I've never heard of AR-V7 and it has never been brought up by oncologists.   My insurance company probably would have appreciated a test for this prior to treatment.    :-)

  • It took me about sixteen weeks or so after starting Xtandi to drive down the PSA to the lowest point since diagnosis, 0.90---but it never again reached such a low point.  Now my

    PSA has been rising slowly in small increments over the past year, and currently is 5.57      So after more than nineteen months on Xtandi, it may be finally losing its efficacy.      The side effects have been rather severe in my case, but I was willing to tolerate them as long as the Xtandi slowed the progression of the PCa.   

    Perhaps giving the Xtandi a little more time to work might help.

    CERICWIN

  • How To Get A Blood Test For AR-V7 If You Have Castrate Resistant Prostate Cancer and are concerned about whether your abiraterone (Zytiga) or enzaludamide (Xtandi) is working -  from the advanced prostate cancer blog:

    tinyurl.com/zeec4p6 

    Joel

  • Joel, what are your thoughts regarding lack of PSA response by >50% after one month?  I know you have discussed this finding in malcare.  

  • I've been on Xtandi since Nov2013, prior was one month on Galeterone.  Been on Lupron since Sep2012.  PSA nadir was 0.07 until Jul 2015,  rising since, PSA doubling time is 4.3 months.  Currently, at 0,54.  Initial diagnosis at 62 was Gleason 9 (5+4) with bone Mets.  I've been actively reading on subject for past four years.  It is not  unusual for Xtandi to have minimal effect after treatment with docetaxel and vice versa.  They both seem to treat the same molecular protein pathway.  I would get in a clinical for Galeterone, I had to drop out after 30 days due to uticaria.  Also Xofigo seems to have good effect on bone metastes.  Best of Luck!

    Roger

  • John Hopkins does it. Call their lab. Get assay form. Fill it out. Ask your onc to take the blood as directed.pack it in type of box they tell you. Directions are specific. Send overnight. Cost is about $120 total for box and postage. We did - found he was negative but the xtandi BACKFIRED ON HIM in just two months and his PSA tripled in just one month. Xtandi is a super Casodex and Casodex can backfire. So he was not ARV7 either. But good to know if you want to take zytiga.

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