May 26, 2015

Clinical Trials--Why Bother?

Editorial Comment

Most clinical trials DO NOT result in a successful drug or treatment being approved by the FDA. Most clinical trials DO NOT provide a benefit for most participants. So why should anybody participate in a clinical trial?

I have participated in several clinical trials. None of them cured me or slowed the progression of my cancer. None of them did any harm, either (so far). I would participate in future clinical trials if they were relevant to my cancer, if I trusted the researchers, and I didn't have to travel too far too often.

Clinical Trials are good at finding out what DOES NOT work. That is an important step. It allows researchers to try something else, go a new direction, or get back to the laboratory and start over. 

I personally hope that there are many more cancer clinical trials in the future. If only one in ten trials is successful, then we need many tens of trials. Every once in a while there is a major breakthrough usually for one type of one cancer. Mine might be next!

Bottom Line
Clinical Trials thrive on numbers. Volunteering to participate helps you, me, everyone else with cancer, and all those who do not yet have cancer. Many trials never get started because not enough of us participate. One of them could have been the breakthrough that would help me--or maybe you.

Larry Axmaker--12 year cancer survivor

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To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Apr 21, 2015

Clinical Trial stopped early for Breast Cancer Drug Ibrance®

Another clinical trial success story
Ibrance® (palbociclib) trials were halted early by its creator Pfizer when it met its primary endpoint—a statistically significant improvement in progression-free survival in postmenopausal women with HR+, HER2 metastatic breast cancer. This has been a particularly difficult cancer to treat.

Pfizer announced in an April, 15, 2015 press release:
IBRANCE was approved by the U.S. Food and Drug Administration (FDA) in February 2015 as a first-line treatment for women with advanced or metastatic estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer. IBRANCE® (palbociclib), in combination with letrozole, is indicated for the treatment of postmenopausal women with ER+/HER2- advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on PFS. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The confirmatory Phase 3 trial, PALOMA-2, is fully enrolled. IBRANCE is not approved for the use being investigated in PALOMA-3 or for any indication in any market outside the U.S.

The trials were conducted in more than 150 global sites. Although the FDA has approved Ibrance®, the Phase III studies are ongoing. The combination of Ibrance® plus letrozole extended progression-free survival by about 50% (from 10.2 months with letrozole alone to 20.2 months with the combination) in the Phase II part of the study.

If you or somebody you know might benefit from this drug, talk to your doctors.

The American Cancer Society (ACS) estimates that more than 230,000 American women will be diagnosed the breast cancer and more than 39,000 women will die from breast cancer this year. This new drug is expected to prolong many lives.

This drug is one of the new generation of highly effective and very expensive drugs. The projected cost of Ibrance® will be $9,850 a month. This is not out of line with other recently approved cancer treatment drugs.

For more information on clinical trials, what they are, where they are, and if you might qualify to participate, go to the National Institutes of Health clinical trials site.

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To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Mar 26, 2015

One Size Fits All—Right Now, But, What If…

The typical clinical trial today involves hundreds or even thousands of volunteers who are fairly similar (have the same cancer with similar stage and similar prior therapy and maybe even similarities in general health). Then two treatments are compared to each other in this large group of patients. If one treatment fares better than the other, that better treatment becomes the new gold standard treatment. That’s good. That’s progress! But it’s certainly not perfect.

So what about the individual patient?
What is lost in this process is knowledge about how these treatments affect individual patients; for example, you. The average benefit seen in a clinical trial is not shared equally by all participants. Some patients are fortunate to have cancers that are particularly responsive to available treatments and these patients may benefit a great deal. Others may benefit a little less and some may not benefit at all. A few may even be harmed by the treatment as they experience unpleasant side effects along with little or no effectiveness.
A clinical trial treatment is judged by how it performed in the entire group of participants and not as much by how each individual patient responded. Over the years, this approach has saved countless lives. In most cases it’s the best we have at the present time. What about the future? What’s on the horizon?

The Big Three New Directions
1 Targeted Therapy. More and more cancer drugs are designed to target specific defects that occur only in cancer cells and not in the normal human body. This is the same process used in creating antibiotics that attack the bacteria and not the human. As a result, antibiotics have been enormously successful. It has been far more difficult to figure out what makes a human cancer cell uniquely different from the regular human cells that it came from. But drugs are now being designed to exploit these newly discovered Achilles’ heels of cancer. For example, Imatinib Mesylate (aka Gleevec) (developed at OHSU) was one of the first such drugs to become mainstream, revolutionizing the treatment of Chronic Myelogenous Leukemia as well as several other cancers.
Targeted drugs have a good chance of being both more effective and less toxic than most drugs currently in use. Targeted drugs are also more amenable to individualized therapy. Since these drugs have a specific target, it is possible to develop tests that examine the cancer and determine if that particular target is present in a specific, individual patient.

2 Personalized Therapy. More clinical trials than ever before are asking patients to consider a biopsy of their cancer as part of the research. For cancers that circulate in the blood this may be possible with just a simple blood sample. In other cases a needle biopsy might be needed to get a sample. Don’t be surprised if you get such a request when you’re contemplating a clinical trial. These tumor samples are being used to better understand which cancers respond to which treatments. Fear of needles aside, this is a good and progressive step in conducting clinical trials and providing benefits for all those with cancer!
It is likely that in the future the multi-thousand patient clinical trials that seek to measure benefit in the entire group may be replaced by smaller studies that focus on subgroups of cancers that have specific treatable defects.

3 Pharmacogenomics. Not only can we not now tell in advance who will benefit from which treatment, we are equally unable to predict who will develop serious side effects. Matching drugs to cancers will require careful biologic analysis of the tumors. Predicting, and therefore avoiding, side effects will require a careful biologic analysis of the whole human being.
While our individual differences are not due only to genetics, many of our differences and those things that make us unique are coded into our DNA. We expect that hidden within that code is the ability to predict how the body will react to various medications and treatments. In the future, we hope to be able to perform very sophisticated laboratory tests that will enable us to predict which treatments will result in the greatest benefit and do the least harm to each individual patient‑‑and for minimal cost. Let’s hope this all happens sooner rather than later!

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To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Mar 9, 2015

Cancer and Clinical Trials—by the numbers

Every once in a while we find it helpful to take a step back from clinical trial results, experimental drugs, and finding a clinical trial to look at some other cancer information. Today it’s taking a look at the big picture—the numbers, or as close to the facts as we can get. 

In the Wide, Wide World
This year 9,000,000 people worldwide will die from cancer and the number is rising. That is 13% of all deaths. The U.S. ranks 58th in the rate of world cancer deaths. That means 57 countries have lower rates of cancer deaths than we do. The rates are much higher in Poland and Hungary and much lower in Mexico, Iran and many other countries. 

There are growing numbers of people in the world with cancer. How can this be with all the improvements we have made in diagnosis and treatment? Well, there are more and more older people throughout the world. The number one risk factor in getting cancer is to get older. And, more people are living longer with cancer. Then there are factors like pollution and smoking, which is still very popular around the world.

Close to Home
14.5 million living Americans have or have had cancer. 1.6 million more will be diagnosed this year and 589,000 will die from cancer. And, of all those individuals, only about 3% (42,000) will ever volunteer to participate in a clinical trial. You can help improve that statistic!

In the U.S. the 5-year cancer survival rate for all cancers was 49% in 1977. It is 68% today—and much higher for some cancers such as prostate (99%). Earlier diagnosis, better treatment, and lower smoking rates have helped. The most common cancers in the U.S. are breast, prostate, and lung. Breast and prostate cancer have high survival rates, lung cancer has a very low survival rate‑‑still.

Over a lifetime your chance of getting cancer of any kind is 37% if you are a woman and 43% if you are a man. You can avoid some cancers (stay out of the sun, don’t smoke) but others seem to just happen. 

How About some $ and Sense?
Cancer is expensive. In the U.S., cancer treatment costs exceed $88 billion each year. Half of that is for Doctor and out-patient Hospital costs. 35% is for in-Hospital treatment and 11% is for prescription drugs. That’s a lot of money to help us stay alive. And costs are going to increase.

Cancer is very common, horrible, expensive, and unpredictable. The numbers in this article won’t cure you, probably didn’t surprise you, and will not likely change any of your behaviors and choices. But you never know…


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To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Feb 14, 2015

Nobody in a clinical trial wants to be given a placebo, whatever that is…

“Placebo” is often used in a negative way. But that’s not necessarily true. Placebos are sometimes used in clinical trials. A placebo is a biologically neutral substance packaged to look like the real drug. Although often referred to as a sugar pill, many placebos are not even pills. They are simply inactive compounds packaged to look, feel, and appear like an active drug. They may be an injection, IV infusion, capsule, a cream, an inhaler, a skin patch, or take any other form that is used by an active drug.

Placebos are used when the purpose of the research is to compare different approaches to treatment. The placebo helps ensure that the study is double blinded which means neither the doctor nor the patient knows which treatment is being administered. Many cancer patients are understandably concerned that they might get a sugar pill instead of a real treatment. This is often the first question the physician researcher hears when a clinical trial is brought up as an option, “Will I get the real thing or just a sugar pill?”
When placebos are used
The fundamental principle that defines when placebos are appropriate is rather simple: if you have cancer, and a treatment that works is available, a placebo cannot be used instead. Period‑‑end of story. Research is not and cannot be about withholding effective treatments from patients with cancer. A placebo can be used in two research situations:
1          There is no effective treatment and the standard treatment would be observation or perhaps supportive treatment (treatments designed to lessen symptoms but not treat the disease).
2          There is an effective treatment and this treatment is being given to all patients in the study. The placebo is being added to the known effective treatment to allow a comparison between the standard treatment and a combination of the standard treatment plus a new drug of unknown effectiveness.

The Placebo Effect (this is kind of weird)
The most mysterious benefit of having a placebo in a study is that placebos actually do work! Now you may think we are completely losing our minds (always a possibility), but it is true! The degree to which placebos work varies considerably depending on what disease is being studied, but it stands to reason that if we are going to devise a fancy, expensive, patented new drug with an unpronounceable name, it should produce results better than a mere sugar pill. According to the American Cancer Society, placebos have an effect on about one in three patients. Often the result is a reported improvement in a symptom or in quality of life. Sometimes it could actually be a new side effect. The mechanisms through which placebos work may represent, to some extent, the importance of the mind-body connection.

A placebo can reinforce patients’ belief that they will get better and so they actually do. In general, placebo effects are seen as symptoms or things people feel. The actual shrinkage of cancer tumors would be extraordinary. Nevertheless, many studies of new cancer drugs look beyond tumor shrinkage and length of life following a cancer diagnosis. They examine quality of life, symptoms of cancer, and side effects of the drug. Placebos allow us to see the true picture of what a new drug can offer beyond what you could get from a sugar pill.
There’s more to learn about the placebo. Watch for the next chapter!

Post Text Here
To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker