Advanced Prostate Cancer Newsletter

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It was announced today that preliminary results from the Phase II STAND trial demonstrates continued and what is described as a robust immune response with Provenge (sipuleucel-T) that continues two years after completing treatment in men with biochemically-recurrent prostate cancer (BRPC). This finding, along with data from the ongoing Phase IV registry PROCEED trial, are being presented at the 2015 Genitourinary Cancers Symposium (ASCO GU) conference.

The STAND study is a randomized, Phase II trial that consisted of two patient study groups designed to eventually allow the possible expansion of the FDA approval for Provenge to men who are still hormone responsive. One study group completed Provenge two weeks before initiation of androgen deprivation therapy (ADT) and the second received Provenge three months after the start of ADT.

As mentioned earlier, Provenge is not currently approved for men with BRPC until they become castrate resistant. This trial looked at this unapproved cohort of men and found that an immune responses was observed in both study arms. It also suggests there may be a greater cellular immune response in patients who received Provenge prior to ADT compared with those who received it following three months of ADT.

This brings me to two comments about Provenge and this data.

1- The measurement of an immune response in these trials is by way of a surrogate marker, one that is generally accepted, but not validated as a marker for prostate cancer survival. This means there is always the potential that the immune response being measured is not predictable of a longer survival time for men with prostate cancer.

2- Given that the immune response seems stronger in ADT naive men we need to wonder if Provenge were given earlier, while men were still either still hormone responsive or even prior to starting ADT, would the actual survival advantage provided by Provenge have been even longer than shown by the trial used to secure FDA approval?
On the negative Provenge was just rejected by National Institute for Health Care Excellence (NICE) which is the equivalent to the United State’s FDA for the UK and Whales.

The question now is will Provenge be around long enough for these questions to be answered? Dendreon’s bankruptcy and now the NICE rejection seem to be building one hurdle after another for the potential of the long term survival of Provenge.

Joel T. Nowak, M.A., M.S.W.

They said we were wrong, but the evidence is already bearing out the sad truth, Between 2011 and 2013, the proportion of men diagnosed with intermediate- or high-risk prostate cancer, based on blood PSA level, increased by 3% per year. Thank you members of the United States Preventive Task Force for realy blowing it and tapping in the nail into the coffins of American men.

In a preliminary study the authors estimate that this trend may translate to 14,000 additional higher-risk prostate cancer diagnoses nationwide, compared to 2011. As we know high risk ptostate cancer often becomes advanced prostate cancer which is in curable and id terminal.

The study authors to point out that these conclusions are preliminary and must be confirmed through further research.

The researchers anaylsed roughly 87,500 men treated for prostate cancer since 2005 found a notable increase in higher-risk cases of the disease between 2011 and 2013. The retrospective analysis of patient data found the proportion of men diagnosed with intermediate- and high-risk disease increased by nearly 6% in those years. While a rise in mortality has not yet been seen, the authors estimated this apparent trend could produce 1,400 additional prostate cancer deaths per year (based on the 2014 estimated number of new prostate cancer cases and the relative survival of patients with low- vs high-risk cancer).

This study will be presented at the 2015 Genitourinary Cancers Symposium, to be held February 26 to 28 in Orlando (Abstract 143).

Joel T. Nowak, M.A., M.S.W.

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There is some really exciting news on the horizon around immunotherapy for advanced prostate cancer. Bavarian Nordic, the pharmaseutical company that has, along with the National Cancer Institute (NCI), been running clinical trials on Prostvac has unoffically let it been known that Prostvac when combined with another investigational immunologic therapy, Yervoy, has helped to significantly extend survival in men with advanced prostate cancer. This finding which will formally be announced this Thursday at the ASCO GU Meeting in Orlando Florida results from a small early-stage trial conducted by the U.S. National Cancer Institute.

This very small study of 30 men was conducted on men with castrate resistant prostate cancer. The trial involved treating the men with the Prostvac vaccine, in addition to escalating doses of Bristol-Myers Squibb Yervoy, an approved injectable treatment for advanced melanoma that works by taking the brakes off the body’s immune system.

They found that on the average, men taking both drugs survived 31.3 months, compared with a predicted survival period of 18.5 months that had been based on historical survival data for older chemotherapy treatments. Among the 15 men who received the highest 10 milligram dose of Yervoy in combination with Prostvac, 20 percent remained alive at 80 months.

What really makes this even more interesting is that Yervoy had previously failed in Bristol-Myers’ own trials to prolong survival in patients with advanced prostate cancer. This was not a combination trial, but evaluated Yervoy as a single treatment.

Yervoy is one of a number of emerging immuno-oncology drugs called PD-1 inhibitors. These PD-1 inhibitors are expected to have greatest effectiveness when used in combination as it was in this trial. The PD1-inhibitors make cancer cells more visible to the immune system, removing their natural camouflage.

Immune therapies hold the potential to change the face of cancer treatment as they support the bodies own, natural systems to fight cancer. As a result they are also blessed with imparting minimal side effects.

Joel T. Nowak, M.A., M.S.W.

Chemotherapy for prostate cancer is still limited to just two drugs, docetaxel (Taxotere) and cabazitaxel (Jevtana). Both of these chemotherapy drugs are taxanes, but they seem to be very different in their mode of action.

A study published online in Clinical Cancer Research, indicates that cabazitaxel might be more effective for some men than docetaxel. Currently, the FDA label requires that a man fail docetaxel prior to being put on cabazitaxel, but it might be more effective for some men to first have cabazitaxel.

Researchers have also found a genomic marker that could help clinicians identify which men might benefit most from cabazitaxel. Men with this marker might benefit from first being exposed to cabazitaxel prior to docetaxel.

“It was surprising to find that cabazitaxel functions differently than docetaxel in killing cancer cells, even though they’re both taxanes,” says the senior author of the paper, Karen Knudsen, Ph.D., Interim Director of the Sidney Kimmel Cancer Center and a professor of cancer biology at the Sidney Kimmel Medical College at Thomas Jefferson University. “It shows that we may not be taking full advantage of this next generation taxane in the clinic.”

Knudsen and colleagues looked at how cabazitaxel worked and concluded that it might be more effective sooner in the treatment protocol. They found that cabazitaxel worked better than docetaxel in human prostate cancer cells lines that were resistant hormone treatment, both in terms of slowing cancer-cell growth and in its ability to kill cancer cells. This might translate to a more effective control of and kill of cancer, which could translate into longer survival.

First author Renée de Leeuw, a postdoctoral researcher in the department of cancer biology at Thomas Jefferson University said that they found that that cabazitaxel and docetaxel have different mechanisms of action and that “This difference in mechanism suggests that we should treat these two drugs less like members of the same family, and more like two distinct therapies that may each have distinct benefits for certain patients.”
To date their research has only been in the lab. Their results confirmed that cabazitaxel was more effective at killing tumor cells than docetaxel.

The research team has also found a molecular marker that would help identify men most likely to benefit from cabazitaxel treatment.

Drs. Kelly and Knudsen are testing their hypothesis in a phase II clinical trial (ABICABAZI NCT02218606) for which they are currently recruiting. Men with metastatic prostate cancer who have not yet been treated with chemotherapy will be given either the second-line hormone therapy abiraterone, or abiraterone in combination with cabazitaxel.

http://www.eurekalert.org/pub_releases/2015-02/tju-nsr021115.php

Joel T. Nowak, M.A., M.S.W.

Feb
18
2015

SAVE THE CDC PROSTATE CANCER PROGRAM

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President Obama’s fiscal year 2016 budget eliminates all funding for the Centers for Disease Control prostate cancer program. Congress has the power to protect the CDC Prostate Cancer program. We ask for your advocacy to protect this life saving program.
Letters and emails sent via Congressional comment pages are effective ways to tell your representative that funding for Prostate Cancer programs matters to you.

There, you will find a sample letter, which you are welcome to copy whole or in part.   Representatives hear from very few prostate cancer survivors and family members so your letter will be surprisingly powerful.

As you probably know, Prostate cancer is one of the most common cancers in America. Almost 30,000 American men die from prostate cancer every year.  And, African American men die from prostate cancer at a rate that is more than twice the rate for white men.  Incredibly, President Obama’s FY 2016 Budget request eliminates funding for prostate cancer activities at the CDC.
Please take a few minutes to visit http://malecare.org/cdc and decide for yourself if you want to support the CDC program for prostate cancer.
Please feel encouraged to email any questions or comments to: darryl@malecare.org
Categories : advocacy
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Researchers performed a randomized, placebo-controlled Phase II trial of men with localized prostate cancer and a rising prostate-specific antigen (PSA) level post-primary treatment. The men were randomized to receive Avodart (dutasteride @ 0.5 mg/day) or to receive a placebo.

All of the men were receiving intermittent androgen deprivation therapy (IADT), which was stopped at month 9 if the PSA level was greater than 1.0 ng/mL. ADT was resumed when PSA increased to greater than or equal to 5.0 ng/mL. The trial end points included calculating the time the men were off treatment, their PSA nadir after 9 months of IADT, serum testosterone and dihydrotestosterone levels, and time to castrate-resistant prostate cancer (rising PSA while testosterone levels remain greater than 50 ng/mL).
The researchers found they had 80 evaluable men who completed one treatment cycle : 49 receiving dutasteride and 38 receiving a placebo.

The median time off treatment for men reaching greater than or equal to 5 ng/mL was 18.6 and 16.7 months for dutasteride and placebo, respectively (p = 0.7600). The median PSA nadir at 9 months was 0.1 and 0.075 ng/mL, respectively (p = 0.4486). There were no cases where a man developed castrate resistant prostate cancer.

This small-scale Phase II randomized controlled trial showed no benefit to the addition of Avodart (dutasteride) to an IADT regimen. However, the trial was too short having the subject men go through only one cycle of IADT. It would have been very helpful if the researchers had extended this trial through a number of additional cycles.

Can Urol Assoc J. 2014 Nov;8(11-12):E789-94.
doi: 10.5489/cuaj.2332

PubMed Abstract
PMID: 25485005

Joel T. Nowak, M.A., M.S.W.