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Through The Fog Of New Cancer Research Information, The Enthusiasm Of Youth Meets The Wisdom Of Elders

by Dr. Len June 05, 2012

I had trouble sleeping this morning, so I got up and took a look at the tweets on my smartphone that focused on yesterday's sessions at the annual meeting of the American Society of Clinical Oncology in Chicago.

 

There were literally hundreds of bits of information that covered the span of sessions, from science to quality of life to other topics of interests. I wondered how much of the information we have heard over the past several days will actually make a difference in the lives of cancer patients in the days and months ahead. And while sitting in a less well-attended session hearing an update on another once promising approach, the sad reality struck me squarely: not much.

 

This is the premier clinical cancer meeting in the country, if not the world. Thousands of doctors and researchers come to this meeting to learn the latest information about clinical cancer research and cancer treatment. There are thousands of abstracts presented and discussed, and constant chatter about the newest drug or the newest test or the newest way to diagnose cancer. The drug companies, the lab test companies, the computer companies are all here to advance their drugs and their tests and their wares. There are receptions, dinners, private meetings all over the place. There are sessions where literally thousands of doctors sit and listen to the top ranked research presentations, which represent the best of our science. There is certainly no lack of buzz, or excitement, or opportunity to learn. This is truly a festival of information about what is new in cancer treatment.

 

And then I go to a session late on Monday afternoon tucked in a back corner of this vast complex known as McCormick Place and hear a group of presentations reflecting on ten years experience with drugs that we thought blocked blood vessel growth to tumors. There are a couple of hundred people in the room, and the presenters acknowledge that the initial promise of those drugs hasn't been realized. In fact, they note, there are even still controversies over how the drugs actually work. But no one is there to give the story prominence, since it is "yesterday's news."

 

I can't help but think about the excitement that surrounded these drugs ten years ago when they were to "great new thing." I recall sitting in one of those megasessions where thousands hung on the words that one of these drugs significantly prolonged survival in colorectal cancer. Then, the news was greeted with sustained applause. Today, there is barely a whisper among those listening to the latest information.

 

I have been coming to this meeting for over thirty years. I have seen concepts and ideas and the next great thing come and go. Among us older folks there is a shield of skepticism that blunts enthusiasm for some of the claims we hear, and helps us understand that through the fog of information that surrounds this meeting, there inevitably is a process that will distill what is important from that which probably won't make a difference. We can't listen to every presentation, we can't absorb all of the information at every presentation, we are not experts in the science of every presentation. There is simply too much to understand and learn. We have to rely on others to advance the ideas that will get the traction that will make a difference in the care and the lives of our patients.

 

I don't mean to sound too negative. These are incredibly dedicated researchers who do this work, and patients and families who make the ultimate contributions by committing to the clinical trials that advance our knowledge. And we have made progress. But sometimes that progress is quick and so clear cut that it makes a difference in practice immediately, and sometimes it is a long slog. Sometimes the initial hopes are borne out by real-world experience and sometimes there are unexpected complications along the way. It times time and experience and expertise to sort all of this out. Patience is a necessary part of the process, yet too few of us realize that.

 

For example:

 

 

  • In a session yesterday presenting about a new class of drugs to treat melanoma, the discussant talks about the fact that she used the first drug in this class in 2000, which did not produce positive effects for a variety of reasons. Twelve years later, the research presented at the session shows that those drugs actually work in treating some patients with melanoma, which is good news. Even more tantalizing is the possibility that by combining this class of drugs with another drug that was reviewed at this meeting last year and was recently approved for the treatment of advanced melanoma we may be able to deal with unexpected side effects of the newly approved drug, which include reactivation of skin cancers and overgrowth of skin cells. You see, the drug we were excited about last year may turn off the melanoma cells (good news), but it reactivated other pathways that led to undesirable effects (not so good news). I have referred to this as the "squishy balloon effect", where you press the balloon one place and it pops out elsewhere. Others call it "whack a mole." Whatever you call it, we are beginning to realize that our bodies live in delicate balances, and our successes in one area can cause problems elsewhere.

 

 

 

  • A trial presented in the megasession (that's the main session of the conference, with thousands of docs sitting in the room listening in rapt attention, since these are the hand-picked major studies deemed of most importance at the conference) discusses a treatment for lymphoma that markedly increases the time it takes for the disease to progress. Also, side effects appear to be less when compared to the current standard therapy. That's good news. But the researchers can't say whether or not the drug improves the overall survival of these patients, and they don't really emphasize that point. We all hope that it does, but time will tell. Notably, this drug was used first in the 1990's--in the old East Germany. It has taken us over 20 years to get here. Perhaps in another 10 years or so we will know whether or not this drug makes a huge difference for patients with lymphoma.

 

 

 

  • Another trial presented in the megasession discusses whether or not men with advancing prostate cancer do better on continuous treatment which decreases the male hormones in their bodies, or whether they would have the same benefit while having that treatment intermittently with perhaps fewer side effects. The researchers conclude that continuous treatment is better for most men. Then, after the megasession, those who are interested in the topic are invited to go to another room and discuss the presentation. In diplomatic terms, a "vigorous discussion" occurs and the tweets fly. I wasn't there, but a trusted colleague tells me the core argument was that some doctors who believe in the intermittent therapy challenged the conclusions of the researchers. Of the thousands of doctors who heard the original presentation, only a relative handful heard the post-presentation discussion. The controversy was recorded on Twitter with a very interesting hashtag: #ProstateBrawl. The study was started in 1995, 17 years ago, and here we are arguing about the results.

 

 

 

Such is the scientific process. As I have written previously, science is not convenient. At the same time, cancer is a wily foe. It takes intelligence, time, patience, fortitude and commitment--among many other qualities--to make progress. The excitement of youth at hearing a new bit of information or the newly presented results of a clinical trial gives way to the wisdom of elders who have seen it all before and have developed a shield of skepticism.

 

Somehow through all of this fog and maze some meaningful information rises to the top, gets recognition, then traction, then dissemination. But for all of the information presented at these meetings, very little survives that tortuous path.

 

So the meeting draws to a close, and thousands of physicians, scientists and others wend their way home which may be in any of hundreds of cities and countries around the globe. They will digest what they have heard, and react accordingly.

 

Unfortunately, many of the folks who actually treat cancer patients in the United States or elsewhere are not here. They will read about some of these studies in peer reviewed journals, or learn about them through the media or through experts who provide information in a variety of ways. Some of the new ideas and treatments will make it in to clinical practice. Many will not. There is simply too, too much to absorb in any practical way.

 

It is a strange and convoluted process, and difficult for a typical person or health professional to understand. Just like springtime, we will all be back here again next year to start the process all over again. And through all of this, bit by bit and piece by piece, we all hope that our patients will be helped by this effort, for that must always be our ultimate goal.

 

Comments

6/5/2012 2:02:50 PM #

Gregory Pawelski

About the only glimmer of light I've seen come out of the ASCO trade show was in your first posting, promising new approach to treating cancer. Yes, it is just the start of the journey, but one that has been going on for decades. In the 1960s, tumor immunology was probably the hottest field in cancer research. Then again, in the early 1980s, with the work of Rosenberg at the NCI with IL-2 and "LAK" and "TIL" cells.

The immune system is obviously important. Major efforts had been made to harness the immune system in cancer therapy. It is a natural approach to cancer therapy. Yet the results had been extraordinarily disappointing, even in comparison to chemotherapy. Then tumor immunotherapy studies were prematurely abandoned during the early 1990s.

It's good to see any resurgence of aggressive cancer vaccine research. Any criticism of this research would be typical of those that favor attempts to identify one-size-fits-all treatments through trial-and-error testing (randomized clinical trial).

Your experience with that late Monday afternoon presentation is disheartening. The possibility of eradicating cancer by selective destruction of tumor blood vessels (angiogenesis) represent an attractive therapeutic avenue. However, it's going to take "combination" anti-vascular therapy to make a difference. "Effective" combinations of biologics.

Among the most sought after attributes of drug combinations is drug synergy. Synergy, defined as supra-additivity wherein the whole is greater than the sum of the parts, reflects an elegant interaction between drugs predicted on their modes of action. While some synergistic interactions can be predicted based upon the pharmacology of the agents, others are more obscure.

Not many medical oncologists understand the scientific method of assay validation and clinical evaluation, based on using real-time, real patient data, under real-world conditions, to guide medical evidence on this. In short, it is a complex and thorough analysis.

Until the controlled, randomized trialist approach has delivered curative results with a high success rate, the choice of physicians (and patients) to integrate promising insights and methods like assays, remains an essential component of research and treatment technology.

An article in the March 29, 2012 issue of Nature presented reasons why some oncology research never becomes a clinical success. What was found was an overall poor quality of published preclinical data, and 89 percent could not be replicated.

"The scientific community assumes that the claims in a preclinical study can be taken at face value," wrote C. Gleen Begley, senior VP at TetraLogic, and Lee Ellis, a professor of surgical oncology and cancer biology at MD Anderson, there is an assumption that "the main message of the (clinical) paper can be relied on...Unfortunately, this is not always the case."

Begley told CNBC, "These are the studies the pharmaceutical industry relies on to identify new targets for drug development. But if you're going to place a $1 million or $2 million or $5 million bet on an observation, you need to be sure it's true. As we tried to reproduce these papers, we became convinced you can't take anything at face value."

Gregory Pawelski

6/14/2012 2:30:59 PM #

Catherine

It can be a hard feeling to hear about breakthroughs in research, then realize we need to wait years upon years to realize the true potential. But there’s something to be said about hope – it keeps the research going, and in small steps (and occasionally large leaps) things can improve.

Catherine

3/13/2013 2:35:28 AM #

catherinalucy


Finally, you have to look at outsourcing as one of many arrows in your quiver.

catherinalucy

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About Dr. Len

Dr. Len

J. Leonard Lichtenfeld, MD, MACP - Dr. Lichtenfeld is Deputy Chief Medical Officer for the national office of the American Cancer Society.

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