A Layman's Perspective on the Role of Metformin in the Treatment of Prostate Cancer

I am neither a doctor nor scientist nor do I have ready access to medical journals. Nor have I ever been accused of being overly academic. When a bona fide research document comes my way I often have difficulty in determining its full scientific value. Accordingly the following information is shared, sketchy though it may be, in the hope that a few others in my situation will be made aware of the potential of Metformin in the treatment of prostate cancer. Another positive outcome would be to trigger responses from individuals who can fill in the blanks.

My initial protocol prescribed by Dr. Myers in 2013 did not include Metformin. In 2014 in conjunction with a few other changes Dr. Myers prescribed a daily dose of Metformin. At the time I described the purpose of this addition as follows: "This drug is a first line treatment for Type II diabetes. It works by suppressing glucose production of the liver. Based on an Internet medical site this drug also "exhibits a strong and consistent antiproliferation action on several cancer cell lines including prostrate cancer cells." This October Dr. Myers quadrupled my prescription Currently my protocol calls for four 500 mg tablets a day, i. e., two each morning and two each evening.

In retrospect I cannot recall an explanation for this rather substantial increase. About the only comment I can recall went something like follows: "Metformin" (pause) "now there is an interesting medical story if ever there was one." As I reflected more on our discussion and mentally chastised myself for not raising a few logical and timely questions, I recalled an Internet audio-visual presentation by Dr. Myers on this topic; a summary of this presentation appears below:

Patients on Metformin:

1.In the treatment of diabetes:

--experienced fewer mortalities from a variety of adult illnesses including heart attacks, strokes and cancers.

--experienced a reduction in diagnoses of all cancers.

2. In the treatment of prostate cancer:

--"Put a lid" on the progression of metastatic prostate cancer in a sizable proportion of patients in a Swiss study.

--(may) reduce the likelihood of developing hormone resistance.

--reduces the development of adverse side effects of hormone therapy.

--prevents the weight gain associated with hormone therapy.

Dr. Myers concluded his presentation with the following prediction (paraphrased):   " I expect Metformin to become a part of any Pca treatment program designed to induce a compete and durable remission."

Addendum January 1, 2015

One of my trusted advisors "Iron Mike" offered the following comments:

"In contrast to Dr. Myers views, however, there was a report just a few months ago based on a meta-analysis of data from nearly 1,000 patients, all of whom had a history of treatment with metformin and all of whom were all newly diagnosed with non-metastatic prostate cancer between April 1, 1998 and December 31, 2009, suggesting no benefit whatsoever from their use of metformin before or after diagnosis with prostate cancer.

Indeed,in that study (see here) a cumulative duration of treatment (before and after diagnosis with prostate cancer) with metformin of ≥ 938 days was actually associated with a roughly threefold increase in risk for prostate cancer-specific mortality.

In all honesty, until we have some data from a large, well-conducted, randomized trial, I think the jury is out on whether metformin has any meaningful clinical benefit in the management of prostate cancer."

When and if I can reconcile the vastly different points of view expressed herein, I will do so.

Addendum January 12, 20i5
Dr. Myers weighed in on the meta-analysis report as follows:

"THAT STUDY IS A POPULATION-BASED STUDY AND AS SUCH PROBABLY NOT WORTH THE PAPER IT IS WRITTEN ON. WE HAVE A PHASE 2 TRIAL SHOWNG A RESPONSE RATE CLOSE TO THAT OF TAXOTERE":
Addendum January 14, 2015
"Iron Mike" responded to Dr. Myers as shown:
"Alas that Swiss Phase II trial was a non-randomized, single arm trial in just 44 patients. As I indicated above, it is "interesting" but hardly "compelling" (in my judgment). Dr. Myers is, of course, entirely entitled to his opinions, but we appear not to be on the same page yet about the potential value of metformin.
My suspicion at this time is that metformin may have value in a particular subset of men with  advanced prostate cancer. The difficulty will be working out how to define and identify that subset."

Addendum January 29, 2015
In a recently released audio-visual Dr. Myers discusses the use of metformin to slow or prevent the return of prostate cancer after complete remission has been achieved by more aggressive forms of treatment. Avodart is  now routinely used for this purpose. Dr.Myers indicates several studies demonstrate metformin shows great promise

 

 

A Heretofore Unaddressed Radiation Side Effect

As  long time readers of this journal will surely agree, I have been preoccupied with one emergency after another  week after week, month after month for far too long. With the most urgent health issues moreorless under control, the time seems right to address the issue outlined below in an email to my UFPTI case manager:

Bladder Control

Two or three times each evening my sleep is interrupted by the need  to empty my bladder  Frequency is not the primary problem however. Each time involves a stop and go fairly lengthy process which takes two or three minutes to complete. I suspect this problem is proton radiation related. It evolved a year or so following treatment, and I have a friend also a UFPTI graduate who is experiencing similar symptoms .How common is this problem? Why does it occur? Our concern is that it will progress rather than resolve.  Is this a problem that should be addressed? If so, how and when? Please feel free to consult with anyone at UFPTI (or elsewhere) that you think may help answer these questions.

After a week or two during which she consulted with Dr. Gud E. Nuff  and one or more of her counterparts, my case manager contacted me by phone at which time the following discussion ensued (broadly interpreted and liberally paraphrased):

Potty Training

CM: During our early years all of us are indoctrinated with the idea that we need to HOLD OUR WATER throughout the night. Woe be unto those who fail to do so.

Pt: This explanation does not account for the onset of the problem at the age of 72 roughly a year following proton radiation. 

Avodart

CM: Dr. Myers may need to increase your dosage of Avodart.

Pt: I do not  intend to ask Dr. Myers to modify my protocol in an effort to resolve my bladder problem.

Anatomical Anomaly

CM: Your problem may be due to an enlarged prostate.

Pt: I have never been so diagnosed. My medical record on file at UFPTI will directly contradict the possibility of an enlarged prostate.

Diet

CM: Your diet may be overly acidic.

Pt: On rare occasions I treat myself to blackened chicken or blackened Ahi tuna. On even rarer occasions my wife over seasons our spaghetti sauce. I assured my case manager this was the extent of our culinary adventurousness.

Liquid Consumption

At the end of the above described give and take, my case manager expressed an interest in my daily intake of alcohol and water. I confessed to a longtime nightly routine of one or two beers just prior to bedtime. I also admitted to the possibility of consuming too little water during the day, especially  here in Texas, because I play two hours of tennis six days a week (sometimes seven). On hotter days it can be difficult to stay hydrated.

At her behest I agreed to modify this pattern on a trial basis. For the suggested three day period, I discontinued my beer drinking routine.and significantly increased my water consumption.The net result? No change. Oddly enough neither of us seemed overly surprised.

 

In the absence of a definitive, plausible answer, we agreed that I should raise this issue during my upcoming appointment with Dr. Myers. I did so with the following result. His response is summarized below in an email to my case manager:

"With considerable confidence and no hesitation Dr. Myers diagnosed my late evening voiding complications as scarification due to radiation. He seemed irritated that radiation treatment centers like UFPTI do not recognize such damage and leave it to unaffiliated clinics like his for follow-up care. This condition is easily controlled. He then prescribed Trental 400 mg twice a day and Jarrow tocosorb once a day. At the end of this discussion he provided me with a copy of a clinical study titled "Randomized, Placebo-Controlled Trial of Combined Pentoxifylline and Tocopheral for Regression of Superficial Radiation-Induced Fibrosis."

 

A week or two later my case manager contacted me by phone with the following responses: (1) In rare instances some of our patients experience symptoms similar to yours that may be due to scarification of the bladder, (2) We here at UFPTI have used Trental from time to time and (3) We apologize for irritating Dr, Myers.

A Modern Day Medical Miracle Begins to Look Possible

The favorable trend accelerates. In addition to low and stable PSAs my endorectal MRI (about which I was very concerned) turned out far better than expected. The 1.1 cm cancerous lesion detected by Choline Scan at Mayo Clinic two years ago shrunk 60 to 70 per cent as calculated by  Dr. Myers. "If the tumor continues to respond in this manner," Dr. Myers opined, " it may be undetectable by your next appointment scheduled for October 28, 2015. Should this occur we will be able to remove Casodex from your protocol." For the record Casodex is the only anti-cancer medication on my treatment plan with noticeable adverse side effects.

Dr Myers seemed genuinely pleased with these results. Truth be known, however, I am uncertain whether he was enthused because of the dramatic improvement in my health and general well-being or self-satisfied with his own modern day medical wizardry. An elegant moment none-the-less shared by two elderly Pca warriors, albeit in all likelihood, from somewhat different perspectives.

Time permitted so I raised the breast development issue. "Easily controlled", he replied, "one mg of anastrozole daily. Please be advised," he added, "so-called man boobs are a common occurrence with older males." Upon reflection  I hesitate to add to my long list of prescription drugs. My inclination at this point is to table the matter for further review and deliberation.

A Routine and Favorable Medical Update

A few weeks ago Dr. Myers slightly modified my treatment plan in response to a concern I expressed about a reduction in my potency.* In response, the reader may recall, Dr. Myers lowered my weekly intake of Casodex from three 50mm capsules to two. I am pleased to report this change achieved its goal. In addition my PSAs have remained low and stable as indicated below:
 March    .365
 April      .256
 June       .26
 July        .22
Looming on the horizon are the following two events:
--On October 22 I am scheduled for an endorectal MRI ordered by Dr. Myers to determine the status of the 1.1cm tumor in my prostate identified by Choline Scan at Mayo Clinic two years ago.
--On October 29 I will have my third (annual) appointment with  Dr. Myers.
Stay tuned.


*I also expressed concern about breast development and tenderness. There has been little if any improvement in this respect. Time permitting I intend to discuss this issue with Dr. Myers on October 29.

Could Be Something Could Be Nothing : Been There Done That : Well Then Welcome Back

The outcome of my full body bone scan is described below in an e-mail to my immediate family and a close friend:

"The radiologist's report reads in part: There is a localized area of increased uptake (of radionuclide) associated with the very posterior aspect of the 9th or 10th rib on the left. There is also a curvilinear increased uptake associated with the region of the trochanter(upper femur) on the left.

The radiologist verbally advised my primary physician, Dr. Hansen, that he detected no clear indication of metastasis. By phone Dr. Hansen explained  the suspicious areas could be the result of earlier bone trauma of one type or another, e. g., fractures or degeneration. In view of my Pca history neither the radiologist nor Dr. Hansen could rule out metastasis and recommended a full body scan six months from now. Incidentally these findings were supported by six standard x-ray views of the spine and pelvic region conducted subsequent to the full body scan."

As the long-term reader with a good memory will readily appreciate, it is not the first time this Pca warrior-veteran has been caught up between the devil and the deep blue sea. And in all likelihood, it will not  be the last.

The next order of business will be an endorectal MRI suggested by Dr. Myers at our most recent routine appointment. This should be completed within the next three or four weeks.

Good News Bad News(?) Edition

As reported in my prior entry Dr. Myers adjusted my treatment plan in response to the concerns I expressed about  reduced sexuality and increased breast tenderness/tissue deveopment  issues. He thought two 50 mg Casodex pills per week rather than three would restore my quality of life. Although too early to quantify, I am pleased to report improvement in both respects. Equally important, if not more so, my PSA continues to remain low and fairly stable as shown by the following data: March .365; April  .256; May .28.

The above good news is overshadowed by the events I describe in the following Patient Portal email to Dr. Myers: "By way of an update you should know that I have developed symptoms alarmingly consistent with Pca metastasis. These symptoms include acute pain in the lower left posterior of my rib cage brought about by vigorous physical activity (i. e., a competitive singles  tennis match). The pain has not subsided since its onset nearly two weeks ago. The affected area is fairly limited in size and scope, but is quite sensitive to pressure and movement. I have an appointment tomorrow with my family physician (a Pca survivor too).  I would appreciate any feedback you care to provide."

Dr. Myers responded  to my concerns  thusly: "Those would be very atypical for bone met symptoms, which rarely have an acute onset and rarely would be sensitive to touch. This is most likely a cracked rib.* A bone scan  and then an MRI of any abnormalities would be definitive." To which I replied: " Thank you so very much for the feedback. I could only hope that you might be willing to provide an opinion without having seen me. My doctor thought I did the right thing to come in for an examination because of my history. He arranged a total bone scan for  next Tuesday. I will keep you informed. Also, I will contact you regarding an MRI. You indicated when we last met that I should arrange a MRI screening prior to our next appointment."

Thankfully, the above exchange of emails drained the developing  drama of much of its momentum. Even so, as has been said in a great many contexts, "It's not over until it's over." Stay tuned.


*Comforting and plausible but wholly contrary to my online research effort.
.

Side Effects Lead to a Minor Change in My Treatment Plan

On March 6, I sent Dr. Myers the following e-mail via the patient portal:

" I have two concerns which I believe warrant your attention. The first of these we have discussed on more than one occasion, but continues to evolve.  My nipples remain quite sensitive and painful to pressure. A new, worrisome development (literally) consists of a checker-shaped and checker-sized disc beneath each nipple. Additionally there has been  a modest growth of soft tissue on either side, more so on the left than the right. I doubt  this condition is noticeable to others, but I need your help in determining when and if corrective action may be indicated.

The second concern involves my sexuality. Within the past four or five weeks there has been a dramatic reduction in my sexual potency.  For perspective if asked to quantify the loss, I would place the figure between  35 and 45 percent.

My top priorities are to arrest the progression of my cancer and extend the quality of my life for as long as possible. My questions are as follows:

--  Is there a change in my protocol that will enable my wife and I  to continue to "have our cake and eat it too?

 --. At age 78 is it time for us to accept the status quo? Is it time to thank our lucky stars that we have had such "a good long run?"

Your assistance on these matters would be particularly appreciated.

Any additional comments or suggestions you care to offer would be most welcome."*

On March 16 Dr. Myers responded as follows:

"Reduce your  dosage of Casodex from thrice weekly to twice a week. This change should help you with your quality of life."*

I would have preferred a more definitive answer. Rather than belabor the point, however,  I chose to interpret Dr. Myers'  response to mean that such a change may well (1) enable my wife and I to return to our customary level of cake eating activity, (2) suspend the progression of my cancer  and (3) stifle any further breast development.

 Accordingly I replied to his proposed treatment modification as shown below:

"I appreciate your responsiveness to these issues. I will make the change and monitor the results. Thanks again."*

***While most of the material in quotes is verbatim, I exercised my author's editorial prerogative here and there.