PSA rising, bone mets, anandron? chemo? Any thoughts please.

[Billy Brag]

Hi Guys

 

I have missed the last few phone ins but am interested in the above discussion -I have been on continuous monotherapy with Eligard plus Zometa but now my PSA has been climbing to 40 and have some bone mets -my Oncologist has prescribed anandron as a second line hormone therapy for a 3 month trial and if no action suggest that I consider chemotherapy as he does not want my PSA to rise anymore -I am in no pain and remail active-whilst I am not keen on chemo I believe it might be better to try it whilst I am fit an healthy -just turned 70 -the only alternative appears to be Zytiga but this is expensive unless chemo is first -interested in any comments or suggestions

 

[Janis Kinne]

Hi Billy

I'm just wondering if youve seen these articles...

Early Chemotherapy for Men Who Are Still Hormone Responsive – For Some It Might Offer Extra Survival

and

A Caution About Yesterday’s Post About Combining Treatments with Chemotherapy

at

http://advancedprostatecancer.net/

 

These are the Dec 6 and 7 2013 postings from Joel Nowak at the Malecare Advanced Prostate Cancer Program newsletter.  They seem to be quite pertinent.

 

All the best

Janis

[alanbarlee]

G'day Billy,

 

A few more thoughts:

 

You and your oncologist might want to discuss a trial switch from Eligard (leuprolide, an LHRH agonist) to Firmagon (Degaralix - an LHRH antagonist), which is injected monthly, with mild discomfort around the injection site for a couple of days. The slightly different mode of action (in switching off the testosterone-producing sequence and starving the PCa of the fuel it needs to grow) might be worth considering. (Monotherapy is known as ADT1).

 

The idea of adding an anti-androgen like Anandron (nilutamide), which blocks testosterone at the prostate cell surface, sounds good to me. This one has the benefit of potentially dropping PSA more quickly than the widely used Cosudex (bicalutamide), which would be particularly relevant if your bone mets were giving you trouble. With either of these you might notice that some side effects of ADT like hot flushes and fatigue may increase, although I didn't notice any of this. (Dual therapy is known as ADT2).

 

A third item to consider is the addition of a 5-alpha reductase inhibitor, which greatly reduces the systemic reduction of testosterone (T) to dihydrotestosterone (DHT), the several-times more active form that the prostate cancer cells takes up. The best one is Avodart (dutasteride), with the alternative being Proscar (finasteride). Well known PCa specialists in the US like Snuffy Myers, Stephen Strum and Mark Scholz are strong advocates for serum DHT testing and Avodart - see Snuffy Myers recent short web video on this. (Tri-therapy is known as ADT3).

 

If a trial (or trials) with the above fails to arrest the PSA climb, then a prompt switch to Taxotere (docetaxel), as suggested by your medonc, sounds like good strategy to me. There are some administering hints that can avoid issues with tolerance and nail damage,e.g. slow infusion, initially smaller weekly rather than larger 3-weekly doses, and using iced gloves and socks during infusion, with arms and legs elevated, in order to restrict blood flow to the extremities.

 

If Taxotere should fail (unlikely), you still have some options, viz Jevtana (carbazitaxel) - a newer related chemotherapy drug (a cell toxin which has increased side effects for some men), or Zytiga (abiraterone), (perhaps preferred on the grounds of minimal side effects), which acts to block testosterone production (by a different mechanism than the ADT3 items above - including inhibiting androgen transfer into the PCa cell nucleus, where the reproductive DNA resides).

 

Beyond these, Xtandi (enzalutamide) - a very potent anti-androgen - is in the pipeline. It's approved for post-chemo use in the USA and Europe (but not yet in Oz). Approval for pre-chemo use is likely to eventually follow, but this option will probably be a bit late for you.

 

I hope this gives you a few items to discuss with your oncologist. It's good to have some kind of strategy / pathway in front of you: a (temporarily) rising PSA doesn't then have to cause you too much anxiety.

 

Feel free to repost (or to ring me) if you'd like to discuss any of this further - and let's all know how you get on after your next appointment.

 

Best wishes,

 

Alan             

[alanbarlee]

Hi again Billy,

 

I just came across a current Medscape article on taxane chemotherapy (Taxotere/docetaxel and Jevtana/carbazitaxel), short extracts from which are copied below to give you a background to my chemotherapy comments above.

 

"Docetaxel and cabazitaxel are the two taxanes which are in clinical use in CRPC. The ability of microtubules to assemble and disassemble is critical for mitosis (cell division)...... and thus targeting microtubules preferentially targets rapidly dividing cancer cells. It also affects AR (androgen receptor) signalling (to the nucleus)...  Docetaxel is the first approved agent outside of hormonal therapy which has a demonstrated survival benefit in CRPC.

Two studies demonstrated the survival benefit of docetaxel in CRPC patients. The TAX327 study showed that docetaxel every 3 weeks plus daily prednisone was superior to docetaxel every week plus prednisone  .....

Cabizataxel is a newer taxane which was selected through pre-clinical studies which found it had the greatest activity against docetaxel-resistant cell lines in vitro and in vivo. However, there is no clear definition of clinical docetaxel resistance. Similarly, the optimal duration of treatment with docetaxel is usually based on physician judgement. In the TAX-327, patients received up to 10 cycles; however it appears that more can be given if patients are receiving a tolerable response. Further, re-challenging patients with docetaxel after the recurrence of CRPC has also demonstrated some clinical success.

The TROPIC study established the role of cabazitaxel as second line therapy in CRPC after docetaxel. This study randomized men with progressive disease during or after docetaxel to receive cabazitaxel plus prednisone......  Cabazitaxel improved overall survival by a median of 2.4 months in this second-line setting. Cabazitaxel had a higher rate of adverse effects, particularly myelosupression...... Side effects of neutropenia and diarrhea were common...... Significantly, 28 patients (8%) in the cabazitaxel group had febrile neutropenia during the study......  Two phase III trials are ongoing: FIRSTANA assesses cabazitaxel prior to docetaxel, while PROSELICA evaluates a lower dose (20 versus 25 mg/m2 in men treated with prior docetaxel".

 

Cheers,

 

Alan
 

[stevecavill]

Billy, have you done any radiation previously?  I had metatstatic disease with bone mets from initial diagnosis.  I've been on Goserelin and bicalutamide (Zolacos) from twelve months.  I have two clear bone mets - lower and upper spine.  Have just completed radiation to prostate and lower spine and will do Sterotactic body radiation therapy (SBRT) to upper spine in February.  This treatment is only considered useful if the number of mets is small - less than 5.  If you research "oligometasteses" you can find info.

Steve.

[Billy Brag]

Hi Everyone

 

Thanks for your responses -have not done any radiation at this stage -understanding it is effective but short term and only for pain relief -a friend had some and it worked for a while

have only started taking the Anandron -main  side effects are mood swings -I guess it will take a while to get used to the medication -I am going to THailand in 2 weeks time where I will stay for 2 months and will have access to a health resort -go there every year and practice qgung,tai chi ,meditation and acupuncture -also have access to western doctors so I have an incentive to see whether complemenary therapies can make my new medication work more effectively -this time last year I stabalised my PSA after a 2 month visit to THailand