May 2010

For decades, scientists and researchers have looked beyond the standard treatments of cancer---surgery, radiation, chemotherapy, and hormone therapy---to try to find new ways of treating the disease. One innovative and promising treatment method received a boost in April 2010 when the U.S. Food and Drug Administration approved Dendreon’s PROVENGE®, a therapy that uses a patient’s own immune system to fight prostate cancer.

PROVENGE® works by inducing an immune response to prostatic acid phosphatase (PAP), which is expressed in most prostate cancers. The “vaccine” is the first FDA-approved autologous cellular immunotherapy for the treatment of prostate cancer, and it is currently approved for treating men who have advanced hormone-resistant metastatic prostate cancer but who have no or minimal symptoms of the disease. In clinical trials, carried out most recently at the Dana-Farber Cancer Institute in Boston, PROVENGE® extended a patient's median survival by 4.1 months when compared to the survival of patients who received a placebo.

“The big story here is that this is the first proof of principle and proof that immunotherapy works in general in cancer, which I think is a huge observation,” said Dr. Philip Kantoff from the Dana-Faber Cancer Institute.

PROVENGE® is unique in the way it is made. The creation of each personalized vaccine consists of several steps. First, a man’s white blood cells are drawn. After the white blood cells are collected, they are shipped to a Dendreon facility where important immune cells are separated out and then combined with a protein often found on prostate tumours as well as a supplement used to boost the patient’s immune system. Once processed, the cells have a greater potential to activate the immune system and to function as a prostate-cancer antigen. In plain words, the vaccine, which is autologous (or created from a prostate cancer patient’s own cells), helps the immune system to recognize and attack prostate cancer cells in that patient’s body and works as an immune cell activator.  Once it’s ready, the vaccine is administered to the patient in three doses that are given approximately 2 weeks apart, although Dendreon states that the “total course of treatment … can be completed in approximately 1 month.”

The significance of the FDA decision is not limited to the fact that a new treatment is now available for men whose prostate cancer has spread in the body and no longer responds to hormone therapy. The process by which PROVENGE® received FDA approval is an important story in its own right. It’s been a rocky and controversial road, one that Dendreon started down in 1999. Along the way, various patient advocacy groups have pushed for the faster approval of drugs and early-stage therapies for terminally ill cancer patients. There was even a pro-PROVENGE® rally and calls for a congressional hearing into the 2007 FDA “decision not to approve PROVENGE®.” All this happened as a result of the FDA sending Dendreon back to the clinic to confirm that the drug could extend patient survival, a delay of approval that occurred even after an FDA advisory panel of outside experts found the drug was safe and had shown "substantial effectiveness." Some cancer patients---and many Dendreon investors---criticized the agency for denying approval of a drug that they said could help critically ill men who had few options.

One of the other options that is available for men with advanced hormone-resistant prostate cancer is the chemotherapy drug called Taxotere®. This drug has become a standard treatment for men with hormone-resistant, metastatic prostate cancer. In the clinical trial TAX 327, completed in January 2006, Taxotere® was shown to extend the lives of men with hormone-resistant metastatic prostate cancer by roughly two or three months. This is less, although not significantly less, than PROVENGE®.

However, a significant deterrence against treatment with the PROVENGE® vaccination is cost. A full course of treatment today costs $93,000 (US). The cost does not seem to have dampened demand for the drug, though, so it may not be available to all who want it. Dendreon reports that it has only enough resources to supply 2,000 patients with personalized vaccines in the next year and that, initially, the treatment will be available only in one of the 50 centres that participated in the clinical trials.

The significance of PROVENGE® is threefold. First, PROVENGE® seems a likely choice for doctors to use before Taxotere®, which is generally begun as a palliative treatment when bone pain or other metastatic prostate cancer symptoms present themselves. PROVENGE® seems to have fewer (and milder) side effects than Taxotere®, so it might be a good first treatment when hormone therapy fails.  (Of course, the vaccine does have side effects, but these, which include, fever, chills, fatigue, and headache, are categorized as mild.)

Second, regulatory agencies, such as the FDA, may learn from the PROVENGE® story and revise the way they evaluate innovative treatments for terminally ill patients.

But the third and strongest case for the importance of PROVENGE® is the treatment’s implications for future progress. Medicine has long struggled to harness the power of the body’s immune system to attack cancer, and now Dendreon has created a drug that does just that, albeit with limited prolongation of life. Still, there is a feeling in the medical community that Dendreon’s PROVENGE® will create a snowball effect, leading to the advancement and fine tuning of other immune therapies at a faster rate of achievement. Already, several drug companies are researching various immune therapy vaccinations for many other types of cancers. While it is too early to know how significant immune therapy will be for the treatment of cancer, people with metastatic cancer hope fervently that the crawl of Dendreon towards the approval of its immunotherapy for prostate cancer will soon become, for other innovative cancer treatments, a fast but safe walk.

For more on immunotherapy in the treatment of prostate cancer, see the article by David L. B. MacQuarrie entitled “Immunotherapy: An Overview.”