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Prostate Cancer and the Engineer (Part 3)

Posted September 28, 2007 12:01 AM by Steve Melito

So what does a retired engineer living in upstate New York know about prostate cancer? Plenty. Dick Leahy's self-study didn't stop with his publication of Prostate Cancer Survival Decisions in 2002. Five years later – and almost nine years after he was first diagnosed with prostate cancer – Leahy continues to test his "double philosophy" of limited response and intermittent treatment.

Limited Response

Most patients, Leahy explains, want their doctors to "hit the cancer with everything they've got". Oncologists oblige, hoping to "knock the cancer into remission and hold it down forever". If this full-force assault fails, however, medical professionals have "nothing left in their arsenal". According to Leahy, a better approach involves a limited response. Understanding that cancer "never dies" is something that most patients don't want to hear, but the disease's penchant for mutation is a fact. By "never putting the cancer under extreme survival pressure", Leahy concludes, doctors can minimize the possibility of "forced mutation" and relapse.

Intermittent Treatment

The second tenet of Dick Leahy's "double philosophy" is the tricky part. Intermittent treatment requires the assistance of a doctor "with enough courage and understanding to write prescriptions" for various cancer-fighting medications. So far, Leahy has cycled through several anti-androgens, chemical compounds which reduce or block male hormones (androgens) such as dihydrotestosterone (DHT). Unfortunately, drugs that reduce DHT can cause the cancer to become testosterone-independent. Similarly, drugs which block DHT can "teach" the cancer to use other chemicals instead. As for cycling through doctors, Leahy is still in search of what he calls a "guru".

Although has used three anti-androgens to the point of failure, he remains optimistic about new treatment possibilities. EstroGel (ASCEND Therapeutics), a medication which the U.S. Food and Drug Administration (FDA) has approved for women (but not for men with prostate cancer) may be worth a trip to Canada. Dutasteride, a prostate-reducing drug sold as AVODART (GlaxoSmithKline), also holds promise - if the FDA changes its ways. According to Leahy, the regulatory agency has approved .5 mg doses for prostate problems, but has allowed human testing of 2.5 mg doses. In Europe, oncologists have administered 5 mg doses of dutasteride and performed tests with 50 – 100 mg doses. With so much testing done at high dosages, Leahy explains, the FDA's .5 mg limit seems "strange".

What You Don't Know CAN Hurt You

When asked for advice, Dick Leahy recommends that men get screened for prostate cancer at age 40 – even if there is no family history of the disease. "You may not know that you have a family history", he explains. If you are diagnosed with cancer, "don't let anybody tell you to delay treatment or to leave the cancer in.". In the meantime, make the most of your life. During his retirement, Leahy has volunteered for organizations such as Junior Achievement, Retired Engineers and Scientists (RESEED), and the Long Island Science Center. He also contributes to CR4 on a regular basis and enjoys solving Challenge Questions.

Editor's Note: This is the last in a three-part series. Part 1 and Part 2 are already available, right here on CR4.

Additional Resources:

http://en.wikipedia.org/wiki/Antiandrogen

http://www.avodart.com/

http://www.estrogel.com/

http://www.estrogel.com/PDFs/EstroGel-Prescribing-Info.pdf

Steve Melito - The Y Files

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#1

Re: Prostate Cancer and the Engineer (Part 3)

09/28/2007 8:27 AM

What are the side effects of blocking testosterone? Do male cancer patients who take antiandrogens experience the loss of muscle mass? If so, that could lead to osteoporosis.

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#2
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Re: Prostate Cancer and the Engineer (Part 3)

09/28/2007 9:29 AM

Hi:

I have concentrated on survival, not on side effects. I've found them to be mostly at nuisance level. Osteoporosis is one exception because I had it forcefully brought to my attention by one oncologist. He started me on Zometa in 2004 without advising me of the risk of predisposition for osteonecrosis, a particularly nasty side effect that includes non-healing (ever) lesions on the jawbone. When I learned of that, as mentioned previously, I dropped biophosphonates and looked for alternatives.

I found that strontium supplements had been successfully tested, mostly in Europe and mostly as strontium ranelate, for many years. It did an excellent job of building bone mass and strength. In this country, I didn't find the ranelate, but started 680 mg per day of strontium as citrate. It may be placebo effect (if so, I don't care) but, over several months, many of the minor pains, in my spine and elsewhere, slowly faded to zero.

If you wish to try it, be sure to continue calcium supplements, but at a different time of day. It's available on the internet at reasonable cost. That may be why there is little interest in the medical community. I have been very satisfied with my experience. Good luck.

Dick Leahy

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#3

Re: Prostate Cancer and the Engineer (Part 3)

09/29/2007 1:57 AM

Hi DickL,

please post here or send direct to me the links and articles on strontium.

I suppose that humans do best if all ingredients that exist in seawater are part of our diet. That is resulting from the time of first "homo" 6 to 1 million years ago when - may be in 2 different phases- our ancestors lived at the seaside. (No other place in very hot Africa at that time and sealevels down despite big global warming so we don't find the fossils that may remain as these are 100m down below todays sealevel)

Strontium as selenium, chromium and other trace elements are not existing in sufficient levels in many soils but in seawater and seafood. And we do not know how much is a sufficient level.

The problem with bisphosphonates as Zometa - which is proven to be powerful to prevent bone metastasis not only in prostate cancer : some % of the patients suffer from severe and non healing bone and gum necrosis especially in the jaws.

But one of the leading experts on prostate cancer, Stephen B. Strum, - see for his book - it is a treasure of information - claims that none of his many patients that are regularly on bisphosphonates suffered from bone necrosis because supporting medication to ensure bone health is preventing this problem.

Any person who is interested in prolonged health should consider additional calcium and Vitamin D3. But be cautious not to take too much of calcium there are vast differences how much a person can tolerate without damage to the kidneys. The D3 is giving protection from many other internal cancers!

The debate on the dosing of vitamine D3 is not yet settled, there are different opinions ranging from 100 to 8000 IU per day, so I estimate that a dosing of 500 to 2000IU will be the best.

Regarding hormone blocking treatments the combined treatments (three medications for a minimum time after reaching undetectable PSA) has proven the best outcome.

In Strums book data are published.

Combine the engineers tendency to be and stay informed with some joy and happiness of life and some luck: this will result in the best possible results.

RR

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Re: Prostate Cancer and the Engineer (Part 3)

09/29/2007 11:35 AM

Hi RR:

I'll try the links:[STRONTIUM-1]

,

[STRONTIUM-2]

,

[STRONTIUM-3]

If I find that they didn't work, I'll send the information to you separately. The third has some practical user advice. The role of strontium is structural, not trace mineral.

I'd be interested in any data that show that combined therapy provides better survival benefit than intermittent use and rotation of antiandrogens, with androgen suppression reserved for after failure of all the antiandrogens. That's what I've been doing for some time now and I've managed to remain among the living, even with my discouraging Gleason = 8 and 10 day doubling time.

I am taking an extra 2000 IU of Vitamin D, in addition to that included with my Calcium supplement and Multivitamin/mineral.

Thanks for the advice. I've enjoyed volunteer classroom work since retirement, but I find little interest in science demonstrations in New York state.

Best regards,

Dick Leahy

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In reply to #4

Re: Prostate Cancer and the Engineer (Part 3)

10/26/2007 1:59 PM

Dear Dick,

I was doing a Google search trying to find the price of the software (Quosa) mentioned by RR on this blog. I often recommend Quosa to patients & physicians to facilitate empowerment. Interestingly, in reading through one of the hits on this search, I came across this site & read through the exchanges between you & others relating to prostate cancer, my area of expertise. I did notice the nice comments made about "A Primer on Prostate Cancer, The Empowered Patient's Guide" and the PCRI (Prostate Cancer Research Institute) website at www.pcri.org.

What I wanted to share with you is that there is a great deal of information on bone health & PC & about strontium in this area. Strontium is a stimulator of the osteoblast, the cell population responsible for building bones. Zometa & other bisphosphonate compounds are inhibitors of the osteoclast, the cell population responsible for resorbing bone. I have used a great deal of bisphosphonates in my treatment of men with PC but also use the following, in conjunction:

(a) comprehensive bone supplement with adequate amounts of absorbable calcium but not in excess of 1,000mg per day. Other factors in such a supplement include magnesium, silica, boron (at least 3mg per day).

(b) Vit K with at least 100mcg of vitamin K2 (menaquinone) per day

(c) Vit D as 25-OH D3 & at the same time use the serum testing of 25-OH D3 to titrate the amount of Vit D-3 taken. The URL for a good lab to do this is http://cas2.questdiagnostics.com/scripts/webdos.wls?MGWLPN=TBCWP65&wlapp=DOS&OrderCode=17306X&SITE=4&SearchString=V%2A&tmradio=title

The average amount of Vit D-3 necessary to achieve a healthy level of 25-OH D3 (60 or high ng/ml) has been 8,000 IU of Vit D-3 per day, in my experience.

(d) Strontium as strontium citrate at a dose of 227mg tid. An inexpensive source for this is http://store.agoodvitamin.com/aorstsu90vec.html & the product is Strontium Support. I have no affiliation with any of the above companies or labs.

(e) Supplementary silica as Biosil. http://www.lef.org/newshop/items/item00371.html carries a brand of biosil. It is also inexpensive.

Other areas often forgotten regarding bone health include the need for resistance exercise & the importance of alkalinization of urine to improve bone density. There is of course peer-reviewed literature on this & using Quosa can facilitate finding medical publications on any of the above. On the PCRI website you can find an old article written by me that is still current on issues of bone integrity as they relate to PC:

http://prostate-cancer.org/resource/pdf/Is2-1.pdf

I hope this helps.

Stephen B. Strum MD, FACP
Medical Oncologist Specializing in Prostate Cancer

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In reply to #5

Re: Prostate Cancer and the Engineer (Part 3)

10/26/2007 3:05 PM

Dear Dr. Strum:

Thank you for your thoughtful response to my message. I learned of osteonecrosis and strontium through the old Don Cooley network, which I believe you contributed to occasionally ..... at least indirectly. At the time, I resented having been started on Zometa without being told of the potential predisposition for osteonecrosis but perhaps it was just a timing problem. In 2004, it was just being reported.

I was recently advised to cut back my calcium to 600 mg/day because of my blood levels. I also increased total vitamin D to 2600 IU/day and I'm awaiting my lab report on 25-OH levels as recommended by Dr. Trump at Roswell. I'll probably be increasing it further. I'm getting traces of the other elements in my multivitamin, but I'll have to check further on the dosages.

My cancer has recently become hormone refractory so I'm always looking for ideas. I received 103 mCi of samarium 153 a couple of weeks ago and was told that it may not effect PSA. I'm trying to determine how that can be when bone scans from other patients clearly show a reduction in metastatic bone lesions.

Thank you for the information about Quosa. That was the first I'd heard of it. I'll try to find if it'll work on my Mac.

Thank you again for the information Dr. Strum and I hope you'll be a permanent participant in CR-4.

Best regards.

Dick Leahy

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In reply to #6

Re: Prostate Cancer and the Engineer (Part 3)

10/26/2007 4:15 PM

Dear Dick,

osteonecrosis of the jaw (ONJ) is relatively new & relatively rare. I have yet to see a case in a patient under my care. There is a paper by Ardine et al on the importance of not allowing calcium levels to drop & stimulate PTH (Parathyroid hormone or Parathormone). I will paste the abstract to the end of this message.

I have not been a big fan of the radioactive isotopes for treating men with PC & bone metastases since I have seen too much bone marrow adverse effects with persistent low platelet counts. You should see a drop in PSA as a result of a salutory effect of Samarium.

Quosa is available for the MAC.

Here is the abstract:

Ardine M, Generali D, Donadio M, et al: Could the long-term persistence of low serum calcium levels and high serum parathyroid hormone levels during bisphosphonate treatment predispose metastatic breast cancer patients to undergo osteonecrosis of the jaw? Ann Oncol 8:8, 2006. [PMID: 16524968]

Osteonecrosis of the jaw (ONJ) is a serious event that uncommonly complicates the natural history of bone metastatic patients treated with bisphosphonates [1]. The pathogenesis of this adverse event is unknown and probably multifactorial [2, 3]. The mechanisms by which bisphosphonates may cause ONJ are unclear. It is commonly believed that bone turnover disruption and angiogenesis reduction in local bone microenvironment induced by these drugs could affect the quality of jaw bone during growth and healing, promoting the development of a non-healing wound and osteonecrosis [1]. Bishosphonates are able to induce hypocalcaemia and hyperparathyroidism [4]; this condition could potentially be contributory. Secondary hyperparahyroidism, in fact, is a major factor responsible for renal osteodystrophy [5]. This condition favours the onset of spontaneous osteonecrosis usually observed in the femoral head region. The possible contributing effect of secondary hyperparathyroidism after bisphosphonate administration to ONJ development has never been addressed. From 2002 to 2005 ONJ has been observed in 13 breast cancer patients (aged between 42 and 75 years) with metastatic bone disease, submitted to zoledronic acid therapy (4 mg i.v. every 4 weeks) plus specific antineoplastic therapies in two Italian Oncology Institutions. All patients also received a 500 mg calcium supplement and 400 IU of vitamin D daily. Median time elapsed from starting zoledronic acid to the ONJ onset was 14 months (range 3-44). Circulating serum calcium was measured every month in all patients and values were corrected for serum albumin. Serum parathyroid hormone (PTH) levels were concomitantly evaluated in the six patients followed in one institution.

Calcium and PTH values obtained at baseline conditions before starting zoledronate and in the 4 months preceding ONJ were compared with those obtained at baseline and from the 12th to 14th month of zoledronate treatment in 40 consecutive breast cancer patients followed in one institution who did not develop ONJ over the subsequent 18 months. As outlined in Table 1, at baseline conditions no difference in serum calcium levels between the two groups was observed; contrast patients destined to develop ONJ had higher PTH levels than controls. ONJ patients showed lower calcium levels and higher PTH values during zoledronate treatment than controls at all time points considered. Many of the differences attained statistical significance.

In the randomised registrative study of zoledronic acid in bone metastatic breast cancer patients [5], increased PTH was observed in the first treatment months, showing a progressive decrease in the subsequent months. This pattern has been confirmed in our control patients, since,after 12 months of zoledronate treatment, serum calcium was normal and serum PTH was only slightly elevated. Patients developing ONJ showed a clear persistence of a condition of relative hypocalcaemia and secondary hyperparathyroidism in the time period preceding this adverse event. These results suggest that persistent hyperparathyroidism may be involved in the complex pathogenesis of ONJ associated with bisphosphonate treatment. Tailoring calcium and vitamin D consumption to each patient, on the basis of serum calcium and serum PTH, could potentially limit the onset of ONJ.

Therefore, I speculate that the reason I have not encountered ONJ in my patients treated with various bisphosphonates over the last 10 years is that I have always employed the use of a comprehensive bone supplement at the same time & have always emphasized the importance of the interconnectivity of all biological systems: the hip bone is connected to the thigh bone but also to the prostate, to the heart, the brain, and so on.

I will not have ample free time to contribute to this forum since I have an active private practice & also I spend pro bono time answering focused questions on PC at an email forum called P2P (patients to physicians) that has been around a long time.

Regards to all.

Stephen

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In reply to #7

Re: Prostate Cancer and the Engineer (Part 3)

10/27/2007 8:16 PM

Dear Dr. Strum:

Thank you for your reply and information. I share your concern about radioactive isotopes but, in my position, the risk balance looks a little different from that of an unbiased observer. Certainly the risk of marrow damage with strontium 89, with its high energy and long half-life did seem high. That's why I decided very quickly to go with the samarium 153 when I learned of it. One series of bone scan images of a patient who had received 4 infusions of samarium at 16 week intervals, showed an impressive reduction in bone metastasis and platelets seem to recover at 8 weeks with the samarium ...... and my list of options is getting pretty short.

There are large gaps in my knowledge of the strontium/biophosphonate tradeoff, but I rely largely on the results of studies such as the one reported in the following abstract:

"Strontium Ranelate: Dose-Dependent Effects in Established Postmenopausal Vertebral Osteoporosis—A 2-Year Randomized Placebo Controlled Trial P. J. Meunier, D. O. Slosman, P. D. Delmas, J. L. Sebert2, M. L. Brandi, C. Albanese, R. Lorenc, S. Pors-Nielsen, M. C. De Vernejoul, A. Roces and J. Y. Reginster Hôpital Edouard Herriot (P.J.M., P.D.D.), 69437 Lyon, France; Cantonal Hospital (D.O.S.), 1211 Geneva 14, Switzerland; Centre Hospitalo-Universitaire (J.L.S.), 80030 Amiens, France; University of Florence (M.L.B.), 50139 Florence, Italy; University of Rome (C.A.), 00161 Rome, Italy; Health Center (R.L.), 04-736 Warsaw, Poland; Hillerød Hospital (S.P.-N.), 3400 Hillerød, Denmark; Hôpital Lariboisière (M.C.d.V.), 75475 Paris, France; Hospital Candelaria (A.R.), 38010 Santa Cruz de Tenerife, Spain; and Centre Hospitalo-Universitaire (J.Y.R.), 4020 Liège, Belgium Address all correspondence and requests for reprints to: Pierre J. Meunier, M.D., Hôpital Edouard Herriot, 69437 Lyon Cedex 03, France. E-mail: . Meunier@lyon151.inserm.fr Abstract The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS) trial was to investigate the efficacy and safety of different doses of SR, a novel agent in the treatment of postmenopausal osteoporosis. A randomized, multicenter, double-blind, placebo-controlled trial was undertaken in 353 osteoporotic women with at least one previous vertebral fracture and a lumbar T-score <-2.4. Patients were randomized to receive placebo, 0.5 g, 1 g, or 2 g SR/d for 2 yr. The primary efficacy endpoint was lumbar bone mineral density (BMD), assessed by dual-energy x-ray absorptiometry. Secondary outcome measures included femoral BMD, incidence of new vertebral deformities, and biochemical markers of bone metabolism. Lumbar BMD, adjusted for bone strontium content, increased in a dose-dependent manner in the intention-to-treat population: mean annual slope increased from 1.4% with 0.5 g/d SR to 3.0% with 2 g/d SR, which was significantly higher than placebo (P < 0.01). There was a significant reduction in the number of patients experiencing new vertebral deformities in the second year of treatment with 2 g/d SR [relative risk 0.56; 95% confidence interval (0.35; 0.89)]. In the 2 g/d group, there was a significant increase in serum levels of bone alkaline phosphatase, whereas urinary excretion of cross-linked N-telopeptide, a marker of bone resorption, was lower with SR than with placebo. All tested doses were well tolerated; the 2 g/d dose was considered to offer the best combination of efficacy and safety. In conclusion, SR therapy increased vertebral BMD and reduced the incidence of vertebral fractures."

That, to me, looks like a very effective agent for improving BMD and reducing fractures. I have not seen comparable data for biophosphonates. I would also be curious to know the overall size of the patient group in which the 13 cases of ONJ occurred and to know how many of that cadre were exposed to a triggering event, such as a tooth extraction, after 14 months of zoledronic acid treatment."

As you can tell, I'm way over my head in this sort of discussion, but I still have to work things out the best I can and make the decisions I need to keep my guinea pig alive. I really appreciate you taking the time to carry on this discussion and I hope that others can benefit. Thanks again for your participation in this discussion.

Best regards.

Dick Leahy

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#10
In reply to #7

Re: Prostate Cancer and the Engineer (Part 3)

06/01/2009 4:57 PM

Dear Dr Strum,

I see your name continues to come up in Internet searches regarding the intersection of prostate cancer and osteoporosis. Typically, the concern is the possibility of osteoporosis in men already diagnosed with prostate cancer. My case is just the opposite. I am almost 59 and was diagnosed with osteopeonia/osteoporosis over five years ago. Just three months ago, I was also diagnosed with "indolent" prostate cancer. My concern is the relationship between calcium and the two diseases. I have been taking Actonel in conjunction with calcium for more than five years now. My bone density is improved (although I now understand that the "quality" of new bone growth may be in question). I have scheduled an appointment with my general practitioner and am scheduled back with the urologist in September for another series of PSA tests/another biopsy. In the meantime I am really unsure whether to continue on with daily calcium supplements or not. Comments? Insights?

Thanks,

Jim Moldovan

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#9

Re: Prostate Cancer and the Engineer (Part 3)

11/23/2008 11:15 AM

Hi Moose, I am Dick Leahy's son. I am sorry to report that my dad passed away on Nov 20 at approx. 6:00 AM. I had seen him the week before and we got to spend some time together. He did not die of cancer, it was apparently a massive coronary. He was not necessarily afraid of dying, he just didn't want to succumb to cancer. So in that regard at least he died successfully staying one step ahead of his cancer, for which I am proud of him. His determination was inspiring. I know he really enjoyed the CR4 site and the sense of community that he had with you and so many of your members. His insight on so many different topics will be missed by me and I'm sure many of the people on CR4 with which he corresponded.Hopefully this reaches you. Thank you for recognizing my dad in your blog.

Sincerely, Mark Leahy

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