I’m the Secretary of the URF Board and a patient of Dr. Catalona. He performed my radical prostatectomy in September 1997. I’ve written in Quest for over 5 years. I study and write and counsel and lecture, but I am not a doctor.
This article began from a discussion with Dr. Oliver Sartor, a respected medical oncologist at Dana Farber Cancer Institute (DFCI)
New Drug Therapies: The Complex Issues
The role of drug therapies is mostly to provide a treatment option when surgery and radiation therapy are less likely to work. The experts on drug therapies are the medical oncologists like Dr. Sartor, who kindly agreed to discuss options and issues with me. This article is guided by our conversation, but these are my views.
The newsletter of one of my favorite support groups recently included information about a new drug option, Avastin. The article cited a reliable medical source, which pointed out that the median patient survival in an FDA clinical trial (It was used with a chemotherapy agent.) was about 5-months, but Avastin can sell for $75,000 an infusion.
Most importantly, Avastin can be prescribed “off-label” (for diseases other than the one in the FDA tests) by our doctors, but may be called “experimental” (not subject to payment) by our insurance companies since it does not have FDA approval for prostate cancer.
Is it moral, a man asked me, for him to try to obtain a couple of months of life, of an uncertain quality, by using these drugs if he can only make the attempt by impoverishing his wife and family?
These drug therapies pose complex medical and financial issues that almost everyone views as highly controversial.
Three New Drugs: Avastin, Taxotere, and Provenge
Dr. Sartor pointed out that a large number of candidate drugs are being studied, however only Taxotere-related treatments are FDA approved at this time for prostate cancer.
Avastin builds on the work of Dr. Judah Folkman who revolutionized cancer treatment with his theory of angiogenesis.
Folkman replaced the prior explanation of the growth of cancer with his view that malignant cells caused new blood cells to be formed, and these new blood cells supported cancer growth. Folkman’s idea was to break these new paths with anti-angiogenesis drugs.
His ideas were eventually accepted after a multi-decade fight, but no perfect drug of this type has yet been found. Most drugs in this category are used in combination with chemotherapy drugs. In addition, many drugs now attempt to break other growth pathways for the cancer cells.
Avastin is used extensively for many different types of cancer at DFCI. It was the first (2004) FDA approved therapy designed to exhibit anti-angiogenesis. The doctors at DFCI have positive opinions of Avastin’s effectiveness.
The key part of the FDA approval letter says that FDA approval is based on the use of Avastin and a chemotherapy agent. The regimen produced an extension of median survival of the patients by approximately 5 months, compared to patients treated with the chemotherapy alone (20.3 months vs. 15.6 months). This improvement in survival is one of the largest ever reported in such a trial.
Peculiarly, the 5-month shift in median survival cited in the FDA report – which is widely publicized – doesn’t apply to the treatment of any patient. It’s only a mathematical construct used by the FDA and drug-developers to portray the data from the trial. This “median” person is half way down the survival-list of people who were in the test. The people for whom the drug didn’t work at all are not represented by the median, and the people who had splendid results are also not represented. For example, a drug that cures 40% of patients but has no effect on the rest of the patients, may have a median survival that is very poor. You may wish to read a short paper called “The Median Is Not the Message” that is available on the Internet. The author, Professor Gould, explains why doctors insisted that he had 8 months to live based on the median, when in fact he lived for 20 years.
There are other medical voices to hear that are much more hopeful than saying that only a few months of life are gained.
Dr. Sartor suggested that I look at the Taxotere work of Dr. Tomasz Beer. The median survival advantage for Taxotere in its trial was only 2.5months, yet Dr. Beer writes: “I think at the present time, Taxotere is clearly the most potent chemotherapy drug in prostate cancer, and it has become a nearly universal backbone for combinations with other drugs. Most of us in the field hope to see that we can build on Taxotere, whether it is with DN-101 (this is the ASCENT trial combining Taxotere with a form of Vitamin D called Calcitriol), or with Avastin, or vaccine therapy, or atrasentan (a receptor antagonist), or many others.”
Dr. Sartor is encouraged by the ASCENT trial. It is now being tested in a larger Phase III trial called ASCENT–II.
Dr. Beer has also studied the use of intermittent chemotherapy. He points out that indefinite administration of chemotherapy is not realistic, and asks whether “holidays” will work. Little data has been available on this topic.
Firstly, he adapts the data: namely, he excludes patients who don’t respond to Taxotere (half the patients don’t respond), and then he adds other patient exclusion criteria including a robust PSA response to the initial treatment.
In this first trial he only worked with 18% of the patients who met all criteria, and agreed to participate. He found that a break of about 4 months was feasible, but the work is clearly preliminary.
Intermittent chemotherapy may lead to much more hopeful long-term outcomes for patients.
Provenge is a vaccine (immunotherapy) strategy to treat prostate cancer.
It has been tested in repeated trials on men with highly advanced cancer and in March, the federal health advisers endorsed it for treating advanced prostate cancer.
A final FDA decision on whether to approve Provenge is expected in May.
Even with highly advanced cases, a group of patients seem to benefit from Provenge.
One study suggested that the vaccine could extend the lives of patients by a median length of only 4.5 months. This result is viewed as scientifically significant although not particularly helpful to individual patients. A larger, ongoing study of Provenge is in progress to verify that it increases longevity of prostate cancer patients.
If approved by the FDA, Provenge would be the first of a new class of therapies designed to stimulate a patient’s own immune system against cancer.
- Statements about living only a couple of extra months, which come from the analysis of the median in FDA drug trials, are clearly misleading to patients and their doctors and should not scare off patients.
- All of these drugs are new and in development, but the field of effective options is rapidly growing.
- At this time, clinical use of these drugs is very confusing. The field has very poor ways of determining who will or won’t respond to various drug therapies. It remains an empirical science in which the results in each patient are assessed. Better methods of matching patients to drugs are in development.
Dreaded Question of Cost
Our national insurance system is too complex for anyone to understand. If one calls Medicare (our largest insurer) and asks for authorization, they say that they can’t authorize anything. They will tell you later about whether they will pay. However, it is believed by those who say they know, that Medicare is much more likely to pay one of our major centers of excellence in treating cancer. This topic is important to discuss with your doctor, but currently the outlook for payment is not bleak and many insured people are being covered.
My Bottom Line
Better drugs are coming. We have to hope that better methods of matching patients to drugs also appear.
I began by telling you of the man who asked me whether use of these drugs with their medical and financial risks is moral. My current answer is that with all the risks, I think that enough progress has been made to surely justify the fight to return to good health.
Feedback is encouraged. Contact Dr. Catalona at www.drcatalona.com (see “contact us”), or send me an e-mail at firstname.lastname@example.org. All 15 prior articles are available on the above Website (Click on Quest Articles and then under my picture).
Click here to read the next article, Clinical Trials:
Sometimes Good, Sometimes Not:
A Very Difficult Decision, by Jules Reichel