Colorectal Cancer Blog

This drug's for you....

Personalized medicine sounds so chic, so sophisticated, so elite.  What can be better than having treatment tailor-made just for me!

The problem with a custom product--whether it is a car, a couch, or a chemotherapy regimen--is that the cost of such a product goes up dramatically.  And sometimes you don't get what you want.  Years ago I knew a woman who had a pair of shoes made by a genuine cobbler.  She was living in London at the time and decided, despite the outrageous cost, that this was her one shot at something truly custom-made.  The good news was that these were the most comfortable shoes she had ever owned.  The bad news is that they were uglier that the north side of a cow headed south, if you know what I mean.  The cobbler molded the shoes to her feet; that is why they were comfortable.  But she had, in her words, "pork-chop feet" that were, to put it kindly, oddly shaped.  The result--weird looking, comfortable, very expensive shoes that sat in the back of the closet, unused.

The CEO of Lilly recently declared that the advent of personalized medicine will usher in a new, more efficient era of drug development.  He notes that the typical drug approved by the FDA is only effective in half of the patients who receive the drug.  Clearly this is an outrage.  Clearly we can do better. 

He further argues that personalized medicine will result in lower drug costs.  This is where I hit a stumbling block.  The process of moving a drug from discovery to market is very, very expensive.  To a large extent those expenses are constant, regardless of the sales potential of the drug.  Personalized medicine means, in part, that once a drug has gone through this entire outrageously long and expensive process, it will only be prescribed for half the number of patients that might otherwise have received it.

This means that patients will, over the next few years, receive fewer and fewer drugs that have no chance of helping them.  This is a wonderful, fantastic development.

What we will all need to watch, though, is the unintended consequence of changing economics in drug development.  As the pool of patients decreases, the price point of the drug must increase in order to offset development costs.  It is wonderful to think that a cancer patient can eventually receive a drug custom-made for their genetic profile.  i can only hope that we can somehow work out the money issues so that drug is, in fact, available and not sitting in the back of the closet like a pair of pork-chop shaped shoes. 

On the horizon....

This past weekend I was in Chicago for the annual meeting of ASCO—the American Society of Clinical Oncology.   A few days before that I attended the largest annual meeting for gastroenterologists—Digestive Disease Week.  These meetings are generally where big, new data is presented, where the latest and best is offered up to the professionals working in the field.

This year, not a lot came out in the area of colorectal cancer.  Some additional information was released about the connection between a particular mutation and the patients likelihood to respond to a particular treatment.  (About 25% of patients have this variation, and they are unlikely to respond to this type of agent.)  Some posters were presented about the importance of multidisciplinary care, or about advances in managing liver metastases.  One even demonstrated that increased side effects to a particular treatment correlates with increased benefit from that treatment. 

I was struck, though, by the amount of energy and resources being poured into this field of study.  One poster session I attended had 25 rows of poster presentations.  These are generally early studies from graduate students and young investigators, and often signal trends in treatment and care.  I met with representatives from three companies who are looking at ways to monitor disease or measure treatment.  One company counts tumor cells in the blood; more than 3 cells from colorectal cancer in a 7.5 ml vial of blood is a bad indicator.  Another looks at a particular compound generated only by colon cells.  If that compound is found outside the colon it means the cancer has broken through and spread outside the colon. 

Clearly, the treatment world for people with colorectal cancer will be very different five years from now—and much better.  I am excited about the brave new world that is looming for patients.

Of course, I have a slightly different vision.  I dream of a day when we can manage to get so many people screened we actually don’t need these new developments.  When the medical community finds a way even to screen for early onset colorectal cancer.  Can you imagine a time when the big cancer meeting has no gastrointestinal track because no one gets the cancer anymore?  That’s a world I can live with.

Just the facts…..

The story is told of a scientist walking down a country lane with a friend.  The friend comments, “Those cows sure are a pretty shade of brown.”  To which the scientist replied, “Well, they are brown on this side.”   The point is, the scientist could not see the other side of the cows and was unwilling to comment on something for which there was no direct observation.

The core of science and medicine is data.  “Evidence based medicine” is the hallmark of the day.  This begs the age old question, though, “What is truth?”

Trying to follow the data in a particular field (say, for example, colorectal cancer) is like watching a tennis match.  A lot of back and forth before anything is decided.

The fact is, scientists are human.  And tests are complicated.  And the right kind of statistical analysis can make the numbers look beautiful.  Much as we cherish the image of a researcher as a rigorous “I can only see this side of the cow” kind of person, the reality is shaped by a lot of factors.

Here are some of the issues faced by science:

--What question to you ask?  Suppose you are eating a nice, juicy apple and I ask you, “Please answer yes or no:  Is that thing you are eating round or is it an apple?”  What kind of data would I get?  Asking the wrong question may result in beautiful data, but the data is likely to be meaningless.  What if you combine two chemotherapy drugs, giving full doses of each?  Will that make treatment twice as good?  Turns out that some combination therapies work better than single therapy. Some work the same.  Some are less effective.  It is all in the balance and combination.  But if you look only at the first question you could conclude that combining therapies doesn’t work.

--How much data is enough?  Good scientists never like to stop accumulating data.  At some point they must, painfully, simply report their findings.  The challenge is being sure you have enough data to make the results meaningful.  We all know that if you flip a coin 10 million times, all things being equal you will get “heads” half the time and “tails” half the time.  We also know that you can flip a coin three times and get “heads” all three times.  Several months ago a report came out that combining some supplements with a particular therapy interfered with that therapy’s ability to work.  A few months later another report came out showing that those supplements actually make the therapy work better.  The difference?  More data.

--Aberrations.  The worst thing to happen in research is to have one or two outliers.  All your data lines up neatly. Your charts look great, your graphs are nice and orderly.  Except for those one or two data points that don’t fit the profile.  It is terribly tempting to dismiss those data points.  To ignore them and hope they will go away.  In all likelihood they are nothing.  Unless they aren’t. 

So data and truth aren’t necessarily the same thing.  I am not saying that scientists are lying.  Despite a few high-profile cases of researchers fabricating data, the vast majority of investigators do what they do because they have a passionate, burning desire to find out stuff.  I do believe, though, that data in and of itself is a trap.  Truth comes from lots of different studies over a long period of time.  We can move medicine forward on data, but should not be confused that we truly understand the truth of all that is happening in the human body.

This weekend is the annual meeting of ASCO:  The American Society of Clinical Oncologists.  This is the meeting where all the new information on cancer research is presented.  Thousands of talks and poster sessions and conversations.  Over 30,000 cancer docs from all over the world.  The news will, no doubt, report on several new findings, on new studies with new data.  A lot of it will be exciting.  And some of it will even represent the truth.

The Cure

I received an email earlier this week asking what the Colon Cancer Alliance is doing in the area of research.  I can’t quite get that question out of my mind.

The actual answer is not tough, of course.  The fact is that we have not done a great deal in this area.  We provide information about clinical trials.  We keep close contact with companies who have products on the market.  We track companies who are working on new approaches.  (In fact, next week I am visiting two such companies to learn more about their work.)  We let patients know about surveys and data collection.  And we have signed on, along with a bunch of other people, to documents calling for more funding to the NIH.

A part of me wants to do more.  I spent eight years (a long, long time ago) as a lab tech in medical research laboratories.  I remember seeing for the first time a machine that could analyze tens of thousands of bits of DNA at the same time, and still get a kick out of looking at gels and scans and data plots.  I also am old enough to remember the initial calls to find a cure for cancer.  The idea was that if we threw enough money at the problem we could find the magic elixir that would slay this beast in all its different forms.

So why isn’t CCA doing more in this area?  The easy answer is this—it is not a good use of our limited resources.  Research is expensive.  The programs that led to current treatments for colorectal cancer cost hundreds of millions of dollars.  Despite the cost, a lot of companies are doing new work in this area.  Earlier this year I attended a meeting at which small biotech companies showcased the products they are developing.  At least a dozen of these companies are working in colorectal cancer.  Each company is spending millions on this development.  In the face of this kind of investment, our efforts would have little or no impact.

Still, we could do more.  We could raise funds for start-up research grants.  In the academic world, young investigators often have a new idea they want to test.  They can’t get funds from the NIH until they have data.  They can’t get data without funds.  At this juncture an investment of $50,000 can be the difference between an amazing new approach being developed and this idea being relegated to a rusty cabinet in a musty closet. 

I keep coming back to screening, though.  In the days of my youth we dreamed of a cure for cancer.  With colorectal cancer, though, we have a better solution—we can prevent over 80% of the cases simply through screening.  In contrast, researchers feel they have made a major breakthrough if they find a new therapy that improves life expectancy by 3%.  So, should we spend our limited resources on getting people screened or should those funds become a drop in the bucket required to get a 3% improvement in outcomes?  The numbers demonstrate clearly where we should invest—in screening. 

I have to say, though, that this leaves me dissatisfied. What about the people who fall outside the screening guidelines?  Do we just abandon them?  What about the people who are already diagnosed?  Do we just say, “Well, why didn’t you get screened?” 

Here is my hope.  I hope that the efforts we are launching will have a major impact on screening rates across the country.  I hope that this changes the way we talk about and think about this disease, and that everyone (including primary care physicians who advise 25 year-old patients with persistent abdominal pain and rectal bleeding to eat more vegetables!) will be better sensitized to colorectal cancer.  I hope every patient will seek out and find a network of support and information that will enable them to take control of their treatment and insist on the latest and best care. 

And while I wish desperately that CCA could be the source of funding for some new approach that will result in the “magic bullet” for this cancer, we simply can’t focus on that right now.  I doubt the magic bullet exists.  I think that if it does exist it will be expensive to find and market.  So we will work on supporting patients, and on pushing screening.  And we will watch some percentage of people grow sicker as they wait desperately for “the cure”, knowing that too many of them won’t make it….

I hate this disease.