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Pinks

Thanks Chuck. Sorry it took a few days to reply. Hope you are doing well and others too here. I appreciate and would like to thank you for writing it up for me. That’s so generous of you. Thank you. 

 

Dad is doing good. No pains and his urine flow normal. The stitches will be opened this week and blood test will be done. It’s been a bit uncomfortable but otherwise no issues. 

 

We will discuss the next steps steps on whether to add chemo or radiation with the onco doctor. He was out of town for a few days. However, I am wondering with orchiectomy done, what’s usually other drugs they give? E.g Zytiga etc. He is taking Casodex right now. And based on the follow up check, doctor will decide on the next set of medications. 

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Charles (Chuck) Maack

Hello again, Pinks! The antiandrogen Casodex or its generic bicalutamide is appropriate to hopefully block adrenal gland androgen/testosterone from accessing your Dad's cancer cells, as I mentioned previously.  I also mentioned I was a proponent of including the 5Alpha Reductase inhibitor Avodart/dutasteride and also explained why.  For what ever reason, and despite some of our top Medical Oncologist specialists in the treatment of advanced and high grade prostate cancer including this medication in androgen deprivation treatment, many physicians don't bother prescribing.  As I also mentioned earlier, and recognizing the amount of Gleason 9 cancer found in your Dad's biopsy, that chemotherapy is important early on.  There are obvious side effects but most men I have exchanged information with have come to tolerate the medication after the first few cycles.  How to deal with them explained here: http://www.theprostateadvocate.com/pdf/CHEMOTHERAPY SIDE EFFECTS.pdf 

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alanbarlee

Hi Pinks,

Adding to Chuck Maack's helpful suggestions (and to my earlier post), you might check out your dad's access in India to enzalutamide (Xtandi in the US) or the newer but similar apalutamide (Erleada in the US). Each of these 'anti-androgen' agents work by blocking access of testosterone and related androgens to the androgen receptor on the cancerous prostate cell surface, and therefore to the cell nucleus, causing it to run out of the fuel it need to survive and divide. These newer drugs are way better at doing this than the older anti-androgen, bicalutamide (Casodex in the US), which Chuck mentioned in the context of targeting total androgen blockade (but which may still be relevant if your dad can't access one of the newer drugs).

Best wishes,

Alan   

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Pinks

Thank you Alan and Chuck. Appreciate your replies. I have sent the information to my sister. She will check with urologist (who is giving Casodex to my dad) and find out if they are available.

 

Update on dad - They have not removed the stitch yet and it may take few more days. He is doing good otherwise. No more backpain. The blood has been drawn now to check the PSA level now (14 days post surgery). Then meet with the urologist for check up. 

 

They are also meeting with the oncologist next month to discuss whether to add the chemo and review his results.

 

I do have a qyestion chemo - I know that you have suggested that. But I would like to know, is it absolutely necessary to give chemo now or wait until PSA fluctuates and then give the chemo? 

 

Not sure what the oncologist will say but early on he was saying chemo will be added later if needed. My sister is going to ask about chemo and see what he says. I heard from my sister that he is a very good onco doctor and had treated 2 family member with advanced colon cancer and advanced esophagus cancer. He administered chemo very nicely and they are doing well right now. Not that it matters as it’s a different cancer but that gives us some confidence that he knows. 

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alanbarlee

Hi Pinks,

 

Chemotherapy  (docetaxel) may be a consideration down the track a bit. If your dad's PSA rises after the orchiectomy (especially if the  doubling time is less than 10 months, then systemic treatment would likely be proposed, in the form of androgen deprivation therapy (ADT) with agents like degarelix ('Anandandrone'), goserelin ('Zoladex') or luprorelin ('Lupron'), It is in this context that 6 rounds of docetaxel ('Taxotere') may be given at the start of ADT - especially with high end Gleason score patients.

 

Beyond that are the second generation ADT treatments like abiraterone ('Zytiga'), enzalutamide ('Xtandi') and apalutamide ('Erleada'), which can be added to the above ADT treatment.

 

It would be good to request testosterone tests to accompany PSA, to help to fill out the picture as the strategy develops.

 

Cheers,

 

Alan     

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Charles (Chuck) Maack

The key is whether PSA drops significantly following the orchiectomy and prescribing of Casodex.  With your Dad's Gleason 9 in several biopsy samples this would appear unlikely.  As Alan made note, IF abiraterone acetate (that shuts down the three areas of testosterone/androgen production - testicular, adrenal glands, AND that which cancer cells produce within themselves) is available in India, that should be prescribed immediately in company with the already orchiectomy and Casodex.  If not available but enzalutamide is available, then prescribing enzalutamide in lieu of Casodex to accompany the orchiectomy.  Again, my personal concern that even if temporarily helpful, will be short lived.  Surgical removal of the prostate gland or radiation to the entire prostatic bed and periphery would have no effect on metastasized cancer in locations already determined elsewhere - they would only possibly reduce the amount of cancer to deal with - and actually would be invasive [procedures to your Dad when not going to help much.  And that brings us back to what to do if the foregoing shows no significant reduction in PSA and imaging identifies same metastasis or growing metastasis - chemotherapy early on wherein the Casodex could also continue to be prescribed.  I AM NOT a doctor, only a prostate cancer patient myself who has spent over 20 years in research and study of prostate cancer and its treatment including email exchanges with top Medical Oncologists who specialize in the treatment of advanced prostate cancer, thus I do not "prescribe" but rather offer considerations to be researched further to determine they make sense. 

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Pinks

Thanks Chuck and Alan. Appreciate your insight. I will have them research and discuss these options. We will come to know about PSA in a day or two. I will update the results. 

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Pinks

Hope everyone is doing well. 

 

Here is a quick update -

 

Dad’s PSA result came back and it’s 12. It was done at 13/14 days after the surgery. It has dropped from 65. The stitches are removed now. Next they are meeting oncologist and urologist (who also manages cancer patients) for follow up appointments and next steps. He is doing well. 

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Pinks

Hi again,

 

I hope all is well with everyone. Winter is here in MN. It has started snowing here last night and getting cold day by day. 

 

The urologist has recommended to stay on casodex and calcium supplements. He gave Zometa through IV (brand name Rokfos - Zolendronic acid - 5 mg/100 ml) 2 days ago. My dad felt a bit feverish the next day but that went away in few hours. He is doing good but he is just bored sitting and sleeping at home. The stitch has been removed but the wound has not completely dried as yet. 

 

He will start Zytiga (Indian version of that drug is Abiraterone acitate - 250 MG) soon. The bottle with 120 capsules is about 30k indian rupees (about US$ 450). Urologist wants to check PSA again in about 1.5 months after the last one and then decide on Chemo. But his plan is to aggressively approach with the chemo. 

 

Question - Should he also be on prednizone (5 mg) while taking Zytiga? I read that sometimes that is added. 

 

We are meeting the Oncologist doctor on 17th and discuss the options with him as well. So more to update once that happened.  

 

 

 

 

 

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Charles (Chuck) Maack

Dear Pinks,

 

I wish I had been aware that your Dad was scheduled for IV of zoledronic acid/Zometa since it is very important that any dental work be completed “before” beginning this bisphosphonate because of the propensity of this therapy to possibly cause osteonecrosis of the jaw/ONJ.  Also, this, and the dosing schedule for Zometa is explained at 12 weeks vs 4 weeks thoroughly here:

BISPHOSPHONATES & DENTAL CONSIDERATIONS Compiled by Charles (Chuck) Maack – Prostate Cancer Activist/Mentor

https://tinyurl.com/3m78ymg

 

The below paper “Role and Precautions” pretty much copies my above paper that is more comprehensive:

Role and Precautions About to the Use of Bisphosphonate Drugs

https://tinyurl.com/yb6h2tmc 

 

As far as prednisone to accompany the administration of abiraterone acetate:

  

Importance of Prednisone - prescribed at one 5mg tablet in the morning and one 5mg tablet in the evening - to accompanying Zytiga/abiraterone acetate:

 

The corticosteroid Prednisone is prescribed to accompany Zytiga/abiraterone acetate in order to guard against hypertension, hypokalemia, fluid retention and liver damage as well as ameliorate increased mineralocorticoid resulting from CYP17 inhibition.

 

Take the time to review this paper regarding the reasoning for Zytiga as well as Prednisone:

https://tinyurl.com/yaaoqms3

 

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Pinks

Thanks Chuck. Can the dental work still be done now? I think Zometa will be an ongoing process. Correct? 

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Charles (Chuck) Maack

Best before but better to get to work on dental work ASAP, particularly if he needs any tooth extractions, before Zometa is causing any jawbone issues.  The concern once Zometa is established in the system is if a tooth is extracted, the space of extraction may not heal, as well as if the jawbone has already been compromised, could cause degradation of the jawbone to also not heal. Also, please look into your Dad being administered Zometa/zoledronic acid every 12 weeks rather than every 4 if every 4 weeks is how he is now scheduled.  The reference info I provided you http://tinyurl.com/p6ey2s5 could be sent to your family to take to your Dad's treating physician if there is any problem.  In your reading what I supplied, take note, too, that a bone supplement should be prescribed. 

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Pinks

Perfect. Thank you so much. You are such a blessing. 

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Charles (Chuck) Maack

 

Dear Pinks,

 

Not intending to overwhelm you with information, but I see it important that you and your family in India are aware of issues that become involved with the administration of zoledronic acid.  Too often even physicians administering this medication are not aware of issues of which they should be.

 

You remarked that your Dad was IV administered 5mg of zoledronic acid.  The usual dose is 4mg administered over at least 30 minutes.

 

Bisphosphonate therapy is generally well tolerated but can be associated with increases in serum creatinine. Therefore, monitoring renal function is required for all patients receiving bisphosphonate therapy. Serum creatinine should be monitored before each dose and treatment withheld until any serum creatinine elevations have resolved to baseline levels. Caution should be exercised when treating patients who are receiving other potentially nephrotoxic therapies. With these simple precautions, intravenous bisphosphonate therapy is safe for long-term use and provides durable treatment benefits.

 

Zoledronic acid has also been shown to reduce skeletal morbidity in patients with both osteolytic and osteoblastic bone lesions 

 

Important that others of your Dad’s medications are checked to make sure the zoledronic acid doesn’t experience adverse interaction with those medications.

 

From: https://tinyurl.com/y9m4bggd

 

“This class of drug (My note: bisphosphonates ie zoledronic acid) provides some protection from osteoporosis by inhibiting osteoclast activity, which breaks down bone, while allowing osteoblasts, which build bone, to continue their function. Together, these two types of cells are important for renewing and remodeling bone throughout life. Most cases of bisphosphonate-associated osteonecrosis occurred after dental surgical procedures and in patients taking chemotherapy and steroids for cancer with metastasis to bone. Although the mechanism of this complication is unknown, a theory suggests osteoclastic activity stimulates the formation of osteoblasts. Without completing the cycle of bone regeneration, old bone tissue loses its blood supply and dies. Likewise, after an extraction, insufficient stimulation of osteoblasts leads to a nonhealing site. Another theory, suggested by Woo, Hellstein, and Kalmar is that inhibition of osteoclastic activity prevents turnover of bone, thus repair of microscopic injuries. The weakened physiology of the bone makes it susceptible to necrosis.”

 

The issues with dental care after several administrations of zoledronic acid are further explained in the above paper.

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Charles (Chuck) Maack

Dear Pinks, 

 

I remain concerned, particularly if you are aware that your Dad has dental issues that should have been addressed before his physician administered the initial zoledronic acid. If your Dad has not dental issues, then there is no problem. The following concerns should ALWAYS be advised to the patient by the treating physician before either bisphosphonates or denosumab as Xgeva are administered.  As I noted in an earlier post, unfortunately too many physicians who prescribe these medications fail to recognize (or acknowledge) this important concern.

   

I contacted a renown Medical Oncologist friend who advised the following that before beginning dental work – particularly after treatment with a bisphosphonate as well as the product denosumab as Xgeva – it is imperative to have a dentist put in writing that it is okay for the patient to have “invasive” dental work such as extraction or root canal.   

 

This is of particular importance if it is known that your Dad needs extractions or root canals (invasive procedures) performed in the near term.  Once he is on continued zoledronic acid he would have to have  stopped the medication and not move to dental work until a dentist provides in writing that it is safe to do so.  If he only requires routine dental procedures wherein only fillings may be required, this is not a problem since the risk of osteonecrosis of the jaw/ONJ does not extend to ordinary dental work. Thus, if your Dad only needs routine, non-invasive dental work such as cleaning out cavities for dental fillings (not root canals!) this is not a problem. If in that cleaning out of cavities it is found an extraction or root canal is needed, as noted above, the zoledronic acid treatment would have to be stopped and no further dental work that would be invasive performed until determined safe with your Dad’s CTx (C-terminal telopeptides of collagen I) level found to be over 150 picograms/ML and the dentist putting in writing that it is now safe.

 

Explanation  here:

https://www.lexi.com/individuals/dentistry/newsletters.jsp?id=april_10 

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Pinks

Hi Chuck, 

 

Once again, thank you so so much for providing these information and reaching out to your contacts. I appreciate it. 

 

I asked my dad (seems like sister was aware of this) if he needs any dental work in future. He said that he had 2 root canal done in the past and don't have any issues right now. Hopefully it stays that way. But it's good to know what to be done if the situation comes to that. 

 

I also asked my dad about 4 weeks vs 12 weeks for zoledronic acid/Zometa, he told me it will be once a year. That's what was written in the drug bottle when he looked it up today. We may have to check on that with the Urologist if it should be administered any differently. 

 

 

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Charles (Chuck) Maack

It appears we move from one concern to another for your Dad  I certainly do not understand this one IV of zoledronic acid to be only "once a year!"  With your Dad experiencing metastases, and the necessity of androgen deprivation medications as well as likely chemotherapy, in my research the infusion of this medication should be on a regular treatment basis as long as the metastases exists.  In the past that infusion was administered as 4mg over at least a thirty minute time-frame every 4 weeks.  More recently it was found in research and trial that this same 4mg could be infused every 12 weeks and be just as effective as the earlier every 4 weeks.  In any event, it does not make sense to only administer this drug "once a year."  Anyone going online and searching for appropriate administration of zoledronic acid for men with prostate cancer administered androgen deprivation medications will find what I have explained as the "appropriate" procedure, as well as prescribing a bone supplement.  My recommendation for the most comprehensive "bone supplement" and where available is explained here: https://tinyurl.com/ovnhbj5 

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Pinks

Thanks Chuck. I will have to check on this as this seems odd. I am glad I brought it up. May be we misunderstood the doctor. But good to know that it should be given at 12 weeks interval with a bone supplement. I will inform them right away. Thanks again ..

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