By Mark Scholz, MD
New prostate cancer drugs come to market quite rarely because the studies mandated by the FDA cost hundreds of millions of dollars. The FDA requires these studies to randomly allocate men into two comparison groups. One group receives the new medicine being tested. The other group gets an ineffective fake, called a placebo. Assuming the study is performed in an acceptable manner, the FDA will approve a new drug for commercial use, only if the men who are receiving the new medicine outlive those treated with the placebo by a specified margin without excessive toxicity.
Finding hundreds of volunteers willing to participate in these types of studies is difficult. The men know there is a chance they will get an ineffective placebo. Who wants to take the chance of getting a sugar pill when facing a life threatening illness? Even so, after having used up all the commonly available treatment options, they become desperate and sign up for the study, hoping to be lucky and receive the real McCoy.
These studies run for years because they are only completed when the majority of the study participants have died from progressive cancer. To get a sufficient number of participants, the supervising companies that organize and run these studies need contractual relationships with a hundred or more study centers. The high costs of these studies are easy to comprehend when you consider the requirement to keep track of all these different patients, at so many different locations, over an extended period of time.
Provenge is one FDA-approved medicine for the treatment of prostate cancer that has managed to overcome all these challenges.
Provenge has a unique mechanism of action that works by strengthening the immune system. Dendreon, the manufacturer, patented a process that harvests immune cells out of the blood by plasmapharesis, a three hour process similar to dialysis. The harvested cells are then taken to a special laboratory and mixed with substances to enhance their aggressiveness against cancer. The same cells are then re-infused back into the same patient.
Provenge’s primary appeal is the low incidence of side effects. However, the treatment, which does not rely on chemotherapy, is so revolutionary that after the first study the FDA forced the company to repeat their study to confirm that the treatment genuinely prolongs life due to skepticism. Once again, the second study showed that the Provenge-treated men were 30% more likely to be alive three years after their treatment compared to the men who received a placebo. Finally the FDA acknowledged the results and gave their nod of approval. As can be imagined, the delay, not to mention the additional cost of repeating the study, vastly increased the development cost of Provenge.
Jevtana, an enhanced form of chemotherapy, is another agent that the FDA approved based on a randomized survival study. However, instead of a placebo, Jevtana was compared to an older chemotherapy called Mitoxantrone that reduces pain but does not prolong survival. 755 men were randomly allocated to treatment with either Jevtana or Mitoxantrone. The survival of men receiving Jevtana was 30% better than the men treated with Mitoxantrone.
The story of how Sanofi-Aventis brought Jevtana, a new type of chemotherapy, to market is equally surprising considering that the pharmaceutical company, took a huge risk because they tested Jevtana in men who were already resistant to Taxotere. (Taxotere is considered the “standard” chemotherapy for prostate cancer.) This approach took industry experts by surprise because historically, men resistant to Taxotere could be expected to respond very poorly to any further chemotherapy. Despite the naysayers, Jevtana was proven to improve survival, even in a treatment-resistant group of patients.
The cost of modern anticancer agents is easier to comprehend when considering the years of study that required the expenditure of hundreds of millions of dollars. Jevtana and Provenge are success stories. Unfortunately, when considering the high cost of these medications we must also factor in the additional cost of the many drugs that have been tested in randomized trials, but failed to show an improvement in survival.
Now that Jevtana and Provenge have been proven to help men live longer, further studies are ongoing to determine how these important anticancer tools can be used in the most optimal way. In particular, their effectiveness may be further enhanced by combining them with other medications or with various types of radiation.
About Dr. Scholz:
A board-certified medical oncologist, Mark C. Scholz, MD, serves as medical director of Prostate Oncology Specialists Inc. in Marina del Rey, CA, a medical practice exclusively focused on prostate cancer. He is also the Executive Director of the Prostate Cancer Research Institute. He received his medical degree from Creighton University in Omaha, NE. Dr. Scholz completed his Internal Medicine internship and Medical Oncology fellowship at University of Southern California Medical Center. He is the co-author of the book Invasion of the Prostate Snatchers: No More Unnecessary Biopsies, Radical Treatment or Loss of Potency. He is a strong advocate for patient empowerment.