The Truth About Provenge

Why you should take Provenge

When the FDA first approved Provenge (sipuleucel-T) for men with metastatic prostate cancer there was a lot of controversy surrounding the benefits, the treatment might provide.  The confusion centered around the concerns that, while a man is taking Provenge it usually does not lower their PSA and sometimes the disease continues to show progression as evidenced on scans.  Additionally, the cost of the treatment and many men’s misunderstanding of the potential survival advantage that Provenge could offer are also offered as reasons not to have the treatment.  

None of these concerns were ever good reasons for rejecting Provenge.  None of these reasons were valid when Provenge was approved and they are still not valid.  

The god news is that over time these concerns have diminished, but sadly there still are people who do not understand the value of the treatment if it is given at the optimal time.  Electing not to take Provenge because it does not lower PSA, does not immediately halt disease progression, costs a lot of money and does not cure the prostate cancer are NOT good reasons because they do not reflect the real value of the treatment.   

PSA and Disease Progression

Probably the most heard concern about why Provenge does not work centers around the issue that in most cases a man’s PSA number will continue to increase while getting the treatment.  I understand how difficult it is for anyone with advanced prostate cancer to go through any treatment and watch their PSA continue to increase.  It has been hammered into our brain that our rising and falling PSA numbers are the best indicators of our cancer health.  

Other than Provenge, all of our other treatments do have a near term effect on our PSA. This is also true of our scans. With every other treatment if it is working we can see if the treatment is working by following our PSA and our scans. This is NOT true of Provenge!

Provenge is a different type of treatment.  Provenge is an immunologic therapy that has a different mode of action than all of our other treatments. Unlike our other treatments it needs time to become effective.   All of our therapies work more quickly than Provenge, but this does not mean that Provenge does not work.  

Provenge does not work the way our other treatments work!  Provenge is not an instantaneous therapy and it usually will not lower or even stop the PSA from continuing to increase, nor will it instantly effect disease progression on scans when it is given, this is the simple truth. However, this does not mean that you will not receive a survival benefit from the treatment.  Receiving a survival advantage is the core reason for taking Provenge and Provenge has been shown in three separate phase III, FDA supervised clinical trials to do just that, provide a survival advantage.  

To understand why Provenge works differently than other treatments it is helpful to understand the process that is used to make Provenge.  Provenge is personalized medicine in the true sense of the word, it is manufactured from a man’s own immune cells, white blood cells.  These cells are modified and sensitized against prostate cancer and then a man’s own sensitized cells are returned to him to fight the cancer.  

The first step is to have a procedure call a Leukapheresis which involves the removal of a small percentage, only about 1%, of a man’s white blood cells (aka - immune cells, dendritic cells, killer cells, T cells).  

This Leukapheresis process involves the use of a port or the use of a line in one arm to remove some blood (just like when you are donating blood) and another line that returns the blood minus the harvested white blood cells.  Once a bag of white blood cells is obtained the bag is shipped to a processing plant where the white blood cells go through a process that sensitives them to “see” prostate cancer cells as cancer that should be eliminated.  The sensitized cells are then shipped back and returned via an infusion to the man who donated them.  

This process is repeated two additional times, with a total of three infusions.  These three infusions are usually completed in just one month. 

Since only 1% of the white blood cells are removed during each Leukapheresis and treated at the processing plant, Provenge will take time to train and sensitize the rest of the immune system, the 97% of untreated cells, to fight the cancer, thus we should not have any expectation of seeing the PSA number declining while Provenge is administered.

Sensitizing and training the entire immune system takes time and yes, the PSA will continue to increase while Provenge is given.  This is scary for anyone with advanced prostate cancer, but you will not die from an increased PSA, especially if you take Provenge while your cancer is still at a relative minimal stage like when we first become castrate resistant.

We have all been trained to monitor our PSA as a biomarker of our cancer’s progression and yes, our disease does progress during this phase of Provenge treatment. Until thereturned, treated white blood cells are able to “educate” the 97% of the untreated cells our disease will progress and our PSA will continue to climb. No question, this is nerve racking and most difficult for all of us. It does take nerves of steel, but the payoff will only come if you are patient.

This is why it is important to have Provenge immediately when you become castrate resistant, while the disease (and the PSA) are at their very lowest point. This does not mean that if you are already castrate resistant you should not consider taking Provenge, it just isn’t as optimal.  

Another complaint that has been raised is he high cost of Provenge.  When Provenge was first commercialized it was the most expensive prostate cancer treatment available.  Since its approval we have many additional treatment protocols that cost more than Provenge.  

When considering the cost of Provenge you need to also remember that it is a personalized treatment made specifically from your own cells and only for you.  Think of Provenge as a custom-made suite as opposed as one you buy off the rack.  

Another bogus complaint cited for not taking Provenge is that it does not extend life.  This is NOT true.  We measure survival advantages through comparative phase III clinical trials, Provenge went through three different phase III clinical trials. Compared to placebo (which is superior to no treatment) Provenge has shown itself to extend survival.  “Provenge delivered a statistically overall survival advantage - nearly 38% more patients were still alive 3 years post treatment in the Provenge group compared to the control.” ( 

This survival advantage might actually not reflect the true potential of Provenge.  Data from the trials was corrupted because some men in the control arm crossed over and took Frovenge (aka APC8015F) which was a frozen version of Provenge.  

The FDA carefully monitors the research protocol besides being actively involved in the actual research design of all clinical trials, including the three phase III trials of Provenge. 

Prior to its approval the FDA included an analysis of data from three separate Phase 3 trials (not one as some believe and is more common in receiving approval) in men with metastatic castrate resistant prostate cancer (Studies D9901, D9902A, and IMPACT). The data from all three studies was then integrated to examine the treatment effect in a larger group of men. 

We can only hope that the scientists at Dendreon are able to develop better tools that will let us know if we are one of those individuals that can benefit from Provenge, until that time all we can do is hope that the statistical advantage will work to our own personal advantage. Again, the best recommendation is to jump on Provenge as soon as you become aware that you are castrate resistant, earlier is better.

Like any other treatment Provenge will not work for everyone. Some of us will not receive any survival benefit, but many of us will. 

Each of us should come to our own conclusion about any treatment available. It is important to we try and wrap our mind around as much information as possible, even when the information is in conflict. It is also important to always keep your mind open to new and additional information. It is our personal job to evaluate what we hear and learn and try and integrate this into what we feel will work for our self. The right answer for one of us is not necessarily the right answer for another. There is no universal right or wrong, just what we are comfortable with for our self.

Joel T. Nowak, MA, MSW wrote this Post.  Joel is the CEO/Executive Director of Cancer ABCs.  He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.