Advanced Prostate Cancer

Selenium is one of those supplements that were are told is good for us and then we are told it is bad for us. Every six months to a year the story and the recommendations seem to change.

According to a study by researchers at Dana-Farber Cancer Institute the University of California, San Francisco higher levels selenium in the blood may worsen prostate cancer in some men who already have the disease, that is today’s latest!

The study results said that a higher risk of more-aggressive prostate cancer was seen in men with a certain genetic variant which is found in about 75 percent of the prostate cancer survivors. Men with this particular genetic variant who also had a high level of selenium in their blood faced a two-fold greater risk of a poorer outcome from their prostate cancer than men with the lowest amounts of selenium. By contrast, the 25 percent of men with a different variant of the same gene and who had high selenium levels were at 40 percent lower risk of aggressive disease. The variants are slightly different forms of a gene that instructs cells to make manganese superoxide dismutase (SOD2), an enzyme that protects the body against harmful oxygen compounds.

The research findings suggest that “if you already have prostate cancer, it may be a bad thing to take selenium,” says Philip Kantoff, MD, director of Dana-Farber’s Lank Center for Genitourinary Oncology and senior author of the study that is published by the Journal of Clinical Oncology on its website now and later will be in a print journal. The lead author is June Chan, ScD, of the University of California, San Francisco.

This study reveals the strong interaction between selenium and SOD2 to influence the biology of prostate cancer. The authors say the current research demonstrated that variations in the make up of the SOD2 gene dramatically alter the effects of selenium on the risk of aggressive prostate cancer.

Selenium is a naturally occurring mineral found widely in rocks and dirt. We believe that small amounts of selenium are essential for good health. Supplemental selenium has been sold and promoted as a means of preventing prostate cancer. These recommendations are largely based on observational studies that found higher risk of prostate cancer incidence and mortality in areas of the country that are naturally low in selenium. Despite this conclusion recent research aimed at confirming the benefits of selenium supplementation have been mixed.

Most recently, the SELECT study, which involved 35,000 men, was halted early when, after more than five years, it showed that the supplements didn’t affect the incidence of prostate cancer.

In this Dana Farber study, researchers examined banked blood samples, DNA, and medical records of 489 male patients diagnosed with localized or locally advanced prostate cancer between 1994 and 2001. Their mean age was 62, and their mean PSA (prostate-specific antigen) measurement was 6.0 ng/mL. About half the men were assessed as having a good disease risk, one-third had an intermediate risk and the remaining one-sixth were at poor risk. The researchers measured the level of selenium in the blood and, using the stored DNA, they determined the SOD2 genotype.

Simply having a high level of selenium was associated with a slightly elevated risk of aggressive prostate cancer. However, the shoe dropper in this study was that the risk was much more strongly affected by the interaction of selenium levels and whether the survivor had a certain variant of the SOD2 gene.

Men with the highest selenium levels and the “AA” form of the SOD2 gene were 40 percent less likely to have been diagnosed with aggressive prostate cancer than the men with same gene form but low levels of selenium. Men carrying the “V” form of the gene, selenium had the opposite effect. In these men, those with the highest levels of selenium in their blood were about twice as likely to have an aggressive type of prostate cancer as was their counterparts with low selenium levels.

“Among the 25 percent of men with the AA genotype, having greater selenium levels may protect against aggressive disease,” the authors concluded. “However, for the 75 percent of men who carry a V allele, higher selenium levels might increase the likelihood of having worse characteristics.”

It is important for you to know to which type of SOD2 gene you have prior to taking selenium supplements. Better yet, do not consider taking a selenium supplement unless there is a very good medical reason.

Since we have been told for years that antioxidants can help people live longer, healthier lives with a lowered risk of cancer these results seem counter intuitive. However, Kantoff says, “There is some precedent to this – research has suggested that antioxidants could be protective if you don’t have cancer, but once you do, then antioxidants may be a bad thing.”

In addition to Kantoff and Chan, other authors of the paper include William Oh, MD, Wanling Xie, PhD, Meredith Regan, ScD, and Miyako Abe, PhD, of Dana-Farber; Meir J. Stampfer DrPH, MD, of Brigham and Women’s Hospital and the Harvard School of Public Health, and Irena King, PhD, of the Fred Hutchinson Cancer Research Center, Seattle.

The work was supported by grants from the National Cancer Institute and several foundations and charitable organizations.

Joel T Nowak MA, MSW

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The FDA did introduce its Critical Path initiative in 2004. But, even these expedited processes have become bogged down. The FDA has responded to the political winds and become cautious after the negative publicity it received from the withdrawals of drugs like Rezulin and Vioxx. The best and most recent delay in the prostate cancer world has been Provenge.

Once a drug passes Phase I clinical trials — which test for high toxicity — and Phase II which defines dosing- why not make it available for general distribution through the NCCN, which has superior access to specialized medical expertise than the FDA. The blunt fact is that no matter how able FDA scientists and physicians are, none of them have the years of experience dealing with particular tumors and particular drugs that specialist, scientists and physicians can bring to this project.

Joel T Nowak MA, MSW

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On June 27, 2009, Gina Kolata’s article in the New York Times on the too safe nature of funding from the National Institute of Health (NIH) struck a chord for many of us. She opens the article with the following, “Among the recent research grants awarded by the National Cancer Institute is one for a study asking whether people who are especially responsive to good-tasting food have the most difficulty staying on a diet. Another study will assess a Web-based program that encourages families to choose more healthful foods.”

Her over all conclusion, despite the forty year war on cancer, most grants funded by the NIH on cancer will not break any new ground or make a difference in anybody’s life.

She then cited the example of one funded project that “asks whether a laboratory discovery involving colon cancer also applies to breast cancer. But even if it does apply, there is no treatment yet that exploits it.” So, who is going to see any positive result?

The NIH has spent $105 billion since President Richard M. Nixon declared war on cancer in 1971. The American Cancer Society, the largest private financier of cancer research, has spent about $3.4 billion on research grants since 1946. Despite all this money having been invested in the war on cancer there has been a shockingly small decline in the death rate from cancer, according to the FDA the gold standard for measuring success.

Some scientists view the grant system as if it were another jobs program, a way to keep research laboratories going year after year. Underlying this concept is an understanding that the labs focus will be on small projects unlikely to take significant steps toward curing cancer. One could almost say that cancer research labs need cancer to remain deadly so that they can remain in business!

However, I must say that in reality we do need to keep these labs open and functioning, other wise we will lose their expertise. Without these labs we would not be training the researchers of the future, but we need to train researchers who can make the next big step forward in curing cancer instead of researcher who reinvent the wheel. Currently the types of grants made and the training of these young researchers are as Dr. Robert C. Young, Chancellor at Fox Chase Cancer Center in Philadelphia and Chairman of the Board of Scientific Advisors, an independent group that makes recommendations to the cancer institute, characterized as oriented more to obtaining funding than to curing cancer! I thought our goal was to cure cancer, I guess I am wrong.
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“These grants are not silly, but they are only likely to produce incremental progress,” said Dr. Young. The institute’s reviewers choose such projects because, with too little money to finance most proposals, they are timid about taking chances on ones that might not succeed. The problem, Dr. Young and others say, is that projects that could make a major difference in cancer prevention and treatment are all too often crowded out because they are too uncertain. In fact, it has become lore among cancer researchers that some game-changing discoveries involved projects deemed too unlikely to succeed and were therefore denied federal grants, forcing researchers to struggle mightily to continue.”

Kolata’s example took one transformative drug, “for breast cancer. It was based on a discovery by Dr. Dennis Slamon of the University of California, Los Angeles, that very aggressive breast cancers often have multiple copies of a particular protein, HER-2. That led to the development of herceptin, which blocks HER-2.

Now women with excess HER-2 proteins, who once had the worst breast cancer prognoses, have prognoses that are among the best. But when Dr. Slamon wanted to start this research, his grant was turned down. He succeeded only after the grateful wife of a patient helped him get money from Revlon, the cosmetics company.”

Even top federal cancer officials say the system needs to be changed.

“We have a system that works over all pretty well, and is very good at ruling out bad things — we don’t fund bad research,” said Dr. Raynard S. Kington, acting director of the National Institutes of Health, which includes the cancer institute. “But given that, we also recognize that the system probably provides disincentives to funding really transformative research.”

Not at all surprising, but the private NGO, The American Cancer Society follows a similarly cautious path. Last year, it awarded $124 million in new research grants, with some money coming from large donors but most from events like walkathons and memorial donations.
Dr. Otis W. Brawley, chief medical officer at the cancer society, has stated that he agrees that the entire cancer research effort is too cautious. “The problem in science is that the way you get ahead is by staying within narrow parameters and doing what other people are doing,” Dr. Brawley said. “No one wants to fund wild new ideas.” A statement like this from Dr. Brawley is scary, why has not he used his position to change this? Talking about it and doing something are two different items.

Some experienced scientists have found a way to offset the problem. They do chancy experiments by siphoning money from their other grants, but I believe that this is wrong. However, the bigger wrong is the system that forces researchers to be devious and deceitful with their funders.

The breath of fresh air in this funding problem is the Congressionally Directed Medical Research Program in the Department of Defense (CDMRP). In this program research proposals are scored up if they are high risk, but can make a significant difference in the field of cancer research. The CDMRP’s orientation could serve as an outstanding model for the American cancer Society and the NIH.

Joel T Nowak MA, MSW

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Is there going to be a competitor to Provenge once it is approved? This is a very interesting question as a second investigational vaccine has shown a significant survival advantage in men with asymptomatic metastatic castration-resistant prostate cancer.

There were just released updated results from a phase II trial of PROSTVAC-VF/Tricom vaccine. The trial had a sample of 122 men and its results showed a median overall survival of 25.1 months for men receiving, compared with 16.6 months for those receiving placebo (hazard ratio, 0.56; P = .006). The results were reported by Dr. Philip Kantoff at the annual meeting of the American Society of Clinical Oncology.

This 8.5-month improvement in survival with the poxvirus-based vaccine comes just months after investigators with the phase III IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial reported a 4.1-month survival advantage with the controversial cell-based vaccine sipuleucel-T, also known as Provenge.

What remains unclear with both trials is what is driving this extended survival, as neither vaccine significantly delays disease progression.

The updated primary end point of progression-free survival was not significantly different at 3.8 months with PROSTVAC-VF/Tricom vs. 3.7 months with placebo (HR, 0.88), confirming a previous finding reported 3 years ago at ASCO. In the Provenge trial, time to disease progression was also not significantly different between the vaccine and placebo (HR, 0.95), Dr. Kantoff said.

“While the PROSTVAC experience is very early in comparison to the Provenge experience, these studies raise the question of how survival can be prolonged in the absence of significant objective responses and changes in early progression rates,” said Dr. Kantoff, chief clinical research officer and chief of the solid tumor oncology division at Dana-Farber Cancer Institute in Boston.

This paradox is confusing as it still remains unclear how immunotherapy actually extends lives without delaying disease progression. We do not have any other experience with cancer vaccines to look at. One of the theories for this is that the vaccine builds up the immune response slowly over time, so one observes a delayed effect, said Dr. Mario Eisenberger, who was invited to discuss the results. It’s also possible that the survival advantage is due to post-vaccine chemotherapy, to controls getting worse in the absence of standard docetaxel (Taxotere) treatment, or to some other post-vaccine variable. Based on a back-of-the-envelope analysis he outlined, neither vaccine offers a survival advantage when compared with matched historical populations who were treated with docetaxel or mitoxantrone (Novantrone) in the TAX 327 trial.

Dr. Eisenberger suggested that future trials should be designed to include the tail of the curve for overall and progression-free survival, and should adjust survival outcomes based on prognostic factors such as prostate-specific antigen or PSA-doubling time at progression, which can profoundly affect survival from that point on. If such an adjustment had been performed in the recently terminated VITAL-1 (Vaccine Immunotherapy With Allogeneic Prostate Cancer Cell Lines) trial evaluating the GVAX vaccine, the negative survival results may have been different “and we would have a nice vaccine for us,” said Dr. Eisenberger, the R. Dale Hughes professor of oncology and urology at Johns Hopkins University in Baltimore.

Baseline characteristics of patients in both arms of the PROSTVAC-VF/Tricom trial were similar, Dr. Kantoff said. The vaccine appeared to be beneficial in all subsets, with perhaps a tendency to benefit those with better prognostic disease. Interestingly, the majority of benefit was observed in HLA A2-positive patients, although these results can be considered only hypothesis-generating in light of the negative primary end point, he said.

Because of progression, only 25% of the 82 patients randomized to PROSTVAC-VF/Tricom received all seven vaccinations, which were co-administered with granulocyte-macrophage colony-stimulating factor and given over a 5-month period. Post trial chemotherapy use is not known, Dr. Kantoff said.

Just like with the Provenge trials the incidence of serious side effects were low in this study. Two patients treated with vaccine withdrew because of a grade 2 injection-site reaction and recurrent lip swelling. Two possible drug-related serious adverse events were reported: one grade 2 pyrexia in the control arm, and one thrombotic thrombocytopenic purpura in the vaccine arm, Dr. Kantoff reported.

The investigators disclosed financial ties with BN ImmunoTherapeutics Inc., a Mountain View, Calif.-based subsidiary of Baviarian-Nordic A/S in Kvistgård, Denmark. The company completed the follow-up for survival status, and has announced plans for a phase III study in collaboration with the National Cancer Institute. Dr. Eisenberger disclosed financial ties with Bristol-Myers-Squibb Co., GenVec Inc., the Ipsen Group, Medarex Inc., Sanofi-Aventis, and Cougar Biotechnology Inc.

Basic story from Elsevier Global Medical News. 2009 Jun 25, P Wendling

It certainly looks as though we are on the brink of seeing cancer vaccines becoming a part of the treatment of the disease. With what we hope will be the FDA approval of Provenge next year and possibly a successful phase III trial leading also to the approval of Prostvac in the near future we might soon be able to add to our minimal array of weapons to fight advanced prostate cancer multiple Immunotherapy options.

On the economic side, having a second approved cancer vaccine will introduce a little competition and help control the cost of Provenge to the patient.

Of course, on the possible would not it be great side of the equation, it might come to pass that combining these potential therapies might also extend life even more. Wouldn’t that be great?

Joel T Nowak MA, MSW

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I know, it isn’t manly to cry and it certainly isn’t manly to admit that you cry. But, you know what, I don’t care. I do have reasons to cry and I don’t care how you respond because crying does help me feel better.

OK, I admit it, I’ve been crying a lot recently, but I have good reason.

I have bee thinking about my life. I often think about the futility of how it progresses and how sometimes it doesn’t. There are so many things that just do not make any sense to me.

I remember when I was a young child and went to the movies to see “Old Yeller.” This was a story about a pioneer farming family who lived out on the American range. The only thing I really remember about the story was the dramatic ending. The family was being attacked by a pack of wolves and the family dog, Old Yeller, sprung to their rescue and fought off the wolf pack.

However, it was not without a significant cost to “Yeller.” The wolves had bitten him and the family was forced to put their loyal defender into confinement. Of course, Yeller developed rabies and had to be put down. I will never forget the trauma when the young boy (I guess I could not help but identify with him) decided to be the “man of the family” as dad seemed not to be present and do the deed. With tears rolling down both his and my eyes the boy aimed his rifle at Yeller and killed him.

I will never forget the great sadness and anger that enveloped my body. Here, this dog saved them to only have them return the favor by shooting him. The injustice of it all, these ungrateful people and this ungrateful and unfair world we lived in just overwhelmed me.

I was with my older brother and knew that I could not allow him to see me cry, so I choked back the torrent of tears that I felt inside and pretended not to care. I was wounded, no I was devastated, but I had to be a man. So I walked out of that theater, feeling terror and great sadness, as a stoic man.

I know that I caused great damage to myself that day. I suppressed my feelings; I denied them as I choked back my tears. And as with many of us it developed a pattern of how we deal with our sadness.

I had looked death in the face and didn’t cry when Yeller died. I also looked death in the face, held back tears when my mother (died from lung cancer), my sister-in-law (died from breast cancer), father-in-law (died from colon cancer) and best friend Dan (died from renal cancer) all within a very short period of time. Then, while actively mourning my father-in-laws death my cat passed away.

I was done and I cried like a baby. I cried for everyone and I cried for myself. I even cried for Old Yeller.

My crying did not bring anyone back, but I remembered all of them. My crying didn’t cure any of my cancers, but it did allow me to understand how I actually felt. My crying honored all the people I had lost and it honored my lost health. It honored my being and it honored my future.

Joel T Nowak MA, MSW

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Please take a few minutes to help elevate OUR prostate cancer
nonprofit, Malecare.

As you know, Malecare started and facilitate this blog as part of our program addressing the needs of men living with advanced prostate cancer. Though Malecare is known as our country’s leading gay men’s cancer support group nonprofit, we are committed to helping ALL men with prostate cancer. Malecare continues to be the only national nonprofit with a clearly stated program for guys with advanced stages of prostate cancer.

Today, we need just a few minutes of your time, to help Malecare achieve the recognition that ALL of our volunteers and participants deserve.

Please go to
http://www.greatnonprofits.org/reviews/malecare and click on the “review” button on the left hand side of the page. Then please fill out your “review” of our work in helping guys and their families via this blog, our in-person support groups (if you attend), our listserv for advanced prostate cancer survivors, our website malecare.org, and our book and articles, etc.

Please don’t feel you need to write long, time consuming reviews. But, your positive “vote” will be helpful in alerting our community that there are LOTS of guys like us out here, and we are helping each other fight cancer and live our lives.

You can email me at Joel@malecare.com or our Executive Director at darrylmit@yahoo.com if you have any questions.

Again, go to http://www.greatnonprofits.org/reviews/malecare to write your review.

Joel T Nowak MA, MSW

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Men with advanced prostate cancer who develop an adrenal tumor will usually undergo laparoscopic adrenalectomy (removal of the adrenal gland) as a treatment method. Just like with prostate surgery. in some situations surgery might not be the best alternative for an individual man.

An individual case was recently completed at the Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan using real-time tracking radiotherapy (RTRT) with a gold marker. This procedure was similar to the prostate radiation treatments some of us have had using gold markers. RTRT is considered one of the possible treatment options to surgery because this system can reduce the adverse effects of organ movement such as that in the adrenal gland or kidney.

A 64-year-old man with hormone refractory advanced prostate cancer with an isolated adrenal metastasis in his adrenal gland was the subject. The man underwent RTRT treatment with an implanted gold marker in the right adrenal metastasis. He experienced no adverse events from the procedure. Even though his prostate cancer did progress, experiencing an elevated prostate-specific antigen (PSA) 8 months post the RTRT treatment, there was no further growth of the right adrenal metastasis before he died.

Conclusion: Even though this study had only one man involved, until further similar studies can replicate the results, RTRT treatment with an implanted gold marker might be feasible for the treatment of isolated adrenal metastasis from malignancies including prostate cancer.

Reference:
Int J Urol. 2009 Apr;16(4):410-2.
doi:10.1111/j.1442-2042.2008.02230.x, Sazawa A, Shinohara N, Harabayashi T, Abe T, Shirato H, Nonomura K.
PubMed Abstract
PMID:19416403

Joel T Nowak MA, MSW

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Senator Arlen Specter (D-PA) introduced S. 914, the Cures Acceleration Network and National Institutes of Health Reauthorization Act of 2009.

The bill has three main components:

1. Establishes a new, independent federal agency, to be known as the “Cures Acceleration Network” (CAN), which would award grants and contracts to accelerate the development of cures and treatments of diseases. Research supported by CAN would focus on translating scientific discoveries from bench to bedside.Funds awarded by CAN would support both the development of medical products and behavioral interventions. Entities eligible for CAN research funding include academic investigators, private industry, and disease and patient advocacy organizations.

2. Reauthorizes the NIH at $40 billion for FY 2010, and such sums as necessary for FY 2011 and FY 2012. Additionally, the NIH extramural conflicts of interest policy would be strengthened, requiring greater financial disclosure from NIH grantees.

3. The National Center for Minority Health and Health Disparities (NCMHD) would be elevated to an Institute, and renamed the National Institute on Minority Health and Health Disparities.

Go Senator Specter

Joel T. Nowak MA, MSW

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A presentation at the ASCO conference in Florida reconfirmed the fact that increased levels of C-reactive protein (CRP) is associated with adverse outcomes (earlier death) in men with castration-resistant prostate cancer (CRPC) treated with docetaxel (taxotere).

The study analyzed the baseline serum samples from 119 castrate resistant (CRPC) men enrolled in 6 phase I or II clinical trials. Out of the sample 91% of the men had metastases and 16% had prior chemotherapy exposure as part of their treatment protocol. Median follow-up was 19.7 months and 89% of the men had died at the time of follow up. In a multivariate model CRP (HR 1.09, p=0.036) was independently associated with survival. The risk of death was estimated to increase 8.7% for every doubling of the CRP.

This study confirms that CRPC patients with higher baseline CRP have worse survival. If you have an elevated CRP you need to insist that your treatment become very aggressive and you should give very serious consideration in enrolling into a clinical trial.

Presented at ASCO by R. Prins, MD, et al. at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) - May 29 - June 2, 2009 - Orange County Convention Center, Orlando, Florida USA.

Joel T Nowak MA, MSW

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As we come to another Fathers Day I do have to acknowledge that not all of us will simply celebrate or commemorate this day in a joyous manner, some of us will grieve. Today may be a day of celebrations, family visits and barbeques, but for many of us it will be a sorrowful, bittersweet, or even agonizing day.

Most of us who read this blog have lost our father, are struggling to stay alive ourselves or are watching their father, spouse or partner struggle to stay alive.

Holidays such as Father’s Day can bring up many feelings besides joy and gratitude; so let us also remember and honor those who on this day struggle with disease, grieve, feel pain or anger.

On a day like this, having cancer, other serious illnesses and also struggling with grief can make all the bad things seem much worse. It is hard enough to be in this position, but being only able to witness other people’s pleasures and joys while not being able to feel the same way, can make our situation feel even worse. Though you may rejoice for the joyous feelings of others, your own pain, fear, and disorientation may be amplified.

For those of you feeling that way today, my heart and thoughts are with you.

I am grateful and give thanks to God, the universe, and my miraculous body for the healing that I have had as well as for the healing you have had.

Happy and Healthful Father’s Day,

Joel T Nowak MA, MSW

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