Dr. William Carroll of the Huntsman Cancer Institute spoke with Science Specialist Ed Yeates for our special report "Utah's Cancer Crusaders." Here are excerpts of the interview.
What Is A Phase One Clinical Trial?
What that means is the National Cancer Institute screens about ten of the new compounds each year for their activity to cure cancer cells. This is done in the test tube. These are natural products, like sea urchins-- to chemical and synthesized products that bear resemblance to some of the anti-cancer drugs we use today.
5% Go To Trial
These go through an intense screening profile for toxicity in animals. Once it goes through those trials and it has some hint that it will be useful in cancer treatment-- and that's only about five percent of the drugs make it that far. And then they become available for some institutions to use in patients.
So phase one study is the use of an experimental medication, one that has not been used previously on humans, to see if it can be safely administered, and for us to find the optimal dose to use in the trials.
Phase one means you're looking at safety first, but while that's occuring, you're seeing the possible efficacy of the drug in treating cancer.
Phase 2 and Phase 3 Trials
Phase one studies are designed for us to determine optimal dose levels of a particular medication, and once that's satisfied then we want to use the phase two trial. That's where we're looking at its impact on the cancer itself. Once that's determined, we use this medication in phase three trials, where we take medication and use it in combination with already approved drugs for particular types of cancer.
New Compounds Less Potent For Non-Cancer Cells
The new generation compounds, are they becoming less potent to normal cells and more potent for cancer cells?
There's no question that the next generation of anti-cancer compounds is going to focus on what's unique about the cancer cell and what distinguishes it from normal cells. That was impossible 10 years ago, before we knew exactly what caused cancer-- that is the genetic programs that lead to a particular cancer cell. Now that we've identified some of these (gene) mutations, we can realistically look at that abnormal bio-chemical pathway. And it's easy for pharmaceutical companies-- if you give them a target-- for them to design a whole new set of compounds that will specifically interact... and spare normal tissue.
Combinations Hold Promise
Does any one component hold the most promise?
I think it's going to be a combination of medications. I think we're going to have to attack the cancer cell from many different directions. And it's going to be this combination that will be effective. Cancer cells can develop a resistance to any one treatment program. So you want to use a combination of different treatments.
"SMART Bombs" For Cancer
What we're using now are something like SMART bombs. What you'll see today is a compound that is specifically targeted to bonding to the cancer cells. And once internalized, it activates the bomb or the toxin in this case, and disables the cancer cell. That's where we're relying on the fact that this little magnet that goes to the cancer cell, specifically seeks out the cancer cell and doesn't bind to normal tissues... It will be a combination of different treatments that will work ultimately in the long run.
Targeting Side Effects & Recurring Cases
We are curing 70 to 80 percent, and that's a conservative figure, of all childhood leukemias in the country. Now that's an improvement of 20 percent...So we're closing the gap on childhood leukemia. Now there are 20 percent of patients who do recur, and that's our target at the Huntsman Cancer Institute, is to develop novel therapies for those patients who do recur. And then, of course, we need to make more specific medications. The cure comes at a cost. There are side effects of these medications. So our goal now is to make these medications more tumor specific and develop new novel therapies for those children whose leukemia's recur.
Children Respond Faster
Do children respond generally faster and better (to treatment) than an adult would?
They do respond faster and better. There's no question that the progress of childhood cancer is remarkably better than it is for most other adult tumors. There're two reasons for that. One is, of course, the cancers that we treat, although they are far advanced, tend to be more responsive to chemotherapy. That's just the way they are. They're very fast growing so they're very responsive to the chemotherapy. And secondly, because we're part of a nationwide network we can put these tumors on clinical trials, where we can find the very best treatments.
Once that's identified, we can use that as a foundation for the next study, which incorporates new medications. And by building on that foundation, we've been able to increase the cure rate from the 15 percent, to the 80 percent that it is today.
End to Leukemia in Sight?
Do you think you'll see an end to leukemia in your lifetime?
...In the 15 years since I've been practicing, we've seen that cure rate go up remarkably. There's no question in my mind that that cure rate is going to go from 80 to 85 to 90 to 95 percent by the year 2010. What we want to do then is focus on adult tumors and take this gratifying result we're seeing in pediatrics and translating that into more common cancers like lung, prostate, and breast cancer.
Consider groping around in the dark, shooting bullets at the cancer, seeing what works and doesn't work. We can actually now understand the genetic blueprint, these acquired mistakes that lead to cancer. Once we understand that, I think progress is going to come at an astonishing rate.
