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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(c) 2012 Tom Beer and Larry Axmaker

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