Q: Welcome to Understanding Cancer.  Today we’re talking to Dr. Skip Burris, director of drug development at the Sarah Cannon Research Institute.  Welcome back, Skip.

A: Thanks.

Q: What I want to do today is explore the different types of cancer therapies that patients might be offered.  And I know that when a patient has an initial consultation, they hear a lot about the different treatment options they may have, and it kind of goes in one ear and out the other.  And so the purpose really is that they have a recapping of that discussion that they can visit and to maybe answer some of the questions they might have.  So I think the first thing I want to ask about is chemotherapy in general.  When you’re talking to a new patient, how do you describe to them what chemotherapy is?

A: And chemotherapy is that word that sounds ominous, that sounds scary, and actually I think back to when I was going through my fellowship in the late ‘80s, that some of the chemotherapy meetings were still held in conjunction with the infectious disease meetings, and we were talking about antibiotics and chemotherapy at the same time.  And really, many of the chemotherapy drugs have come out of the same research that brought us antibiotics, that brought us the drugs that kill bacteria and viruses.

So chemotherapy is just simply a medicine that’s going to get inside of a cell and cause it to die.  You know, no different than Penicillin working against the bacteria that invade your lungs or another part of your body, that these chemotherapy drugs, potentially with more side effects, and we need to manage those, and much stronger in terms of their ability to kill cells, but they get inside these cancer cells and interfere with their ability to divide and cause them to die.

Q: Now, while the chemotherapy is attacking the cancer cells, does it also attack the cells, I mean, the body’s normal cells?

A: Well, and that’s the trick to managing the dose and the schedule for the chemotherapy drug.  So the simplest way to think about it is chemotherapy is going to be killing cells that are dividing rapidly, so cancer cells are dividing too fast.  That’s what makes them a cancer cell.  So that’s part of the target for the chemotherapy.

And then you think about the side effects of chemotherapy.  It tends to be those other cells that are still growing and dividing when you’re a fully grown adult.  So that’s why we see some hair loss.  Not with all drugs, and certainly there’s more drugs nowadays that don’t have the hair loss associated, but that’s why you’ll see hair loss.  Your hair’s growing every day, and the chemotherapy drug will get into those hair cells.

That’s why the blood counts will go up and down.  Our bone marrow is our factory that’s making these red cells and white cells and platelets that keep us from bleeding, and the chemotherapy gets into the bone marrow and interferes with the production of those cells, causes those cells to die, so your blood counts will go up and down as well.

And then lastly, the mucosal membrane, so that lining of our mouth all the way down through our gastrointestinal tract.  We’re constantly making a new lining to that organ, turning over those cells, and so that’s why sometimes you’ll see some mouth sores and sometimes you’ll see some of the gastrointestinal toxicity that you see with chemotherapy.

Q: I think of the decade of the sort of late ‘80s, early ‘90s as the decade of supportive care improvements.  So, you know, we developed these new chemotherapy compounds in the ‘70s and ‘80s, and they had all these side effects, and then we spent a decade, in essence, developing ways to reduce the side effects.  And it seems the net effect of that is chemotherapy is really much more tolerable today than it used to be.  I’m curious, what side effects are most treatable or manageable today?

A: So you brought up an interesting point about getting drugs to be able to be tolerable, and nausea was our first big hurdle.  So we had some very good drugs that have come along to help treat nausea, and in fact I joke nowadays that in fact if you’re still having nausea with your chemotherapy, you probably need another doctor or another nurse taking care of you.  You should be able to take care of that side effect.

We have great medicines.  The medicines work a couple different ways.  And actually, some of the medicines that work the best actually tell your brain that you’re not nauseated, and you don’t have that reaction to the chemotherapy.  It’s interesting now, it’s funny, in our clinic one of our battles now is to not have patients eating in the chemotherapy room.  So it used to be nobody wanted to think about food—

Q: [Laughs.]

A: –and now we’ve got to be careful for the smells and the tastes that are showing up there.

Q: Interesting.  What about the effect on the blood cell counts?  Can that be prevented or treated?

A: That can be, and I think we need to be careful and yet aggressive about that.  There’s been news out there [late] about how much we should push the drugs that will help keep our red count up.  So your red blood cells carry oxygen.  That’s when we commonly hear the phrase of somebody being anemic or having low blood.  And really keeping up the red count, keeping up your hemoglobin hematocrit is very, very important.  It helps to make the therapies work better and it’s really probably one of the primary reasons why patients feel fatigue.

I think that that’s an important part of the therapy.  Doctors need to continue monitoring that.  And while any therapy can be overdone, using those drugs that can support the red blood count, the erythropoietin compounds, very, very important to avoid blood transfusions where possible and to keep your energy level up where it can be appropriate.

The other factors that we have now that’s really important is the white cell stimulator.  So these are drugs that in fact cause the white blood count to increase, Filgrastim and Pegfilgrastim, these drugs that will cause the white count to come back to normal more quickly, or actually, in some cases, avoiding from going too low.  The white cells are your important infection fighting mechanism, and anything you can do to keep your body strong, to keep infections away from the side effects of chemotherapy really will be a better outcome for the patient.

Q: Also isn’t the rate of the white blood cell recovery after you give somebody chemotherapy something that’s important to control in terms of the overall management of the patient?

A: It is.  I think that we look at it with using white cell stimulators, using the Filgrastim and Pegfilgrastim compounds, trying to use something like that to avoid infection is one part.  But you hit a key part there, too, where in terms of being able to give your therapy on time.  If your counts are slow to come back and we have to delay your therapy for a week, that’s not good for treating your cancer.  Part of successfully treating cancer is getting that regimen on time and getting rid of those cells as quickly as possible.  So that sort of support so that your blood counts are ready for the next treatment is a key component.

Q: Are there any patient populations that are more likely to have problems with their blood counts than others?

A: So as you age, just quite naturally, your bone marrow as a factory or as a garden that’s making all these white cells and red cells, begins to age, and like any other organ in your body, so your bone marrow is not as cellular, not as active.  So patients, as they get older, need to be carefully considered for use of these agents.  And I certainly think patients over the age of 65, over the age of 70, are very key folks to consider for that.

I also think we need to look at patients that have co-morbid conditions, patients that have diabetes or arthritic problems or other situations where getting too weak, having your blood counts too low, getting a secondary infection, those are important places also to avoid having your counts get too low.

And then lastly, a point we often forget about, is many of our patients are able to continue working through their chemotherapy.  I think continuing to work, in addition to the economic advantages, certainly is good for your state of mind.  I mean, just keep on with your life, keep doing what you’re doing.  So keeping your white blood count up improves the energy level, less susceptible to infection, and often makes you feel like going to work and decreases the risk of being around other people in the work place.

Q: Now, we didn’t mention platelets, which is the third blood element.  I know that a low platelet count, or thrombocytopenia, isn’t a very frequent complication of chemotherapy, but it does occur.  Is there anything that can be done about that?

A: So low platelets, a difficult issue.  As you mentioned, it’s not as common as seeing the red count and the white blood count be lower.  But in fact if the platelet count gets too low, the physician worries about bleeding, and that can be a delay in getting your next treatment.  That’s something you like to avoid.  And doctors don’t like to give platelet transfusions to patients if they can avoid it at all.

There are several research initiatives underway.  There is an approved growth factor that will stimulate your platelets to come back.  There’s been some side effects, some flu-like syndromes with that particular growth factor, so it hasn’t been as popular as we’d like, but it can be used in certain scenarios.  But there’s a whole group of new drugs that are out there now for treating thrombocytopenia, low platelets, in patients that have that as a primary disorder.  And we’re beginning to see research with those drugs after chemotherapy to see if we can keep the platelet counts from going down as well.

Q: These are the drugs that are currently being used to treat what we call chronic ITP?

A: Correct, ITP, idiopathic thrombocytopenia purpura, a condition in and of itself, probably due to your immune system, and your platelet counts drop very low.

Q: Okay.  So it seems over the past several years there’s been significant progress in controlling nausea and vomiting, and managing the blood count side effects.  What about hair loss or effects to the mucosal membranes which you mentioned?

A: So, you know, for patients undergoing fairly intense treatments, there are growth factors out there to ask your doctor about which can help the recovery of the mucosal membrane and slow down some of the effects in that direction.  So we actually do have some supportive care treatments that can help recovery.  For example, those patients that might be getting radiation in addition to their chemotherapy, you know, not having that significant mucositis or mouth sores that might hinder your ability to eat and drink.

Alopecia – the biggest thing that’s happened in that regard is really looking at newer ways of giving drugs or giving the chemotherapy drugs and formulations where they’re less sensitive to the hair.  So we’re a little behind in that.  That’s a, to some patients, a cosmetic issue.  To other patients it can be a little more life altering.  But I think we’re beginning to see more and more effort with the development of chemotherapies, as we understand how they work, to put them in preparations or formulations where maybe we can minimize the effects on the hair.

Q: So nothing’s really been created yet that can prevent hair loss?

A: No, nothing that’s—

Q: No.

A: –nothing that actually will stop that.

Q: Okay.  So one thing I’ve noticed is that when patients are receiving chemotherapy, they’re somewhat reluctant sometimes to mention symptoms they may be having to their doctors.  How important is it for them to really bring to your attention whatever it is they’re experiencing?

A: Very important, and I think you’re right.  Patients are hesitant to have their dose reduced or have their dose delayed.  And, you know, the fact of the matter is everybody handles drugs a little differently.  There’s recommendations, not firm parameters, on the amount of drug that should be given to a patient.  And I think the physicians need to hear from the patients what sort of side effects they’re experiencing.

What’s the appropriate dose for one patient might need to be dropped 20% in another patient, so communicating that, where you want the patient to be as healthy as they can, as strong as they can, and have their energy level up while they go through the therapy.  And sometimes dose reductions and dose adjustments need to be made, and that’s very, very important, and patients shouldn’t be hesitant to administer it.  Doctors aren’t going to withhold care or give an inappropriate dose.  They’re looking to give the right dose and the right schedule to each patient.

Q: And perhaps even more relevant, at some level, is there are things that can help patients through their side effects, but if they don’t bring them to your attention, you really can’t do anything.

A: Exactly.  And what might be a number that makes one patient feel weak or tired might not be so for another patient.  All very, very individualized, and I think that communication is very, very key.  There’s a lot of things out there to help patients with regard to helping support their blood counts, helping control their nausea, helping to stimulate their appetite, and only through communication, only mentioning the symptom enables the doctor or nurse to know to prescribe the medicine.

Q: Well, Skip, thank you for your time today, and we really look forward to having you back.

A: Thank you.

[End of recording.]

Q: Welcome to Understanding Cancer.  Today we’re visiting with Dr. Skip Burris, who is the director of drug development at the Sarah Cannon Research Institute in Nashville, Tennessee.  Dr. Burris has extensive experience in new drug development as well as clinical trials in general, with a focus on oncology.  Welcome.

A: Thank you.

Q: One thing I think that confuses patients is there are several phases of clinical trials.  You hear about Phase I, Phase II, Phase III, Phase IV clinical trials.  Could you sort of concisely walk us through the difference between a Phase I, II and III clinical trial?

A: So a Phase I trial is essentially for patients whose…their tumors have not responded to standard therapy.  So these patients have been through traditional treatment and their tumors haven’t shrunk or gone away.  So their doctor considers them an appropriate candidate and they’re motivated to look at additional treatment.

So these are brand new drugs, different mechanisms of killing cancer cells, and the purpose of the trial is to really, to look at what’s the safest route and what’s the most efficacious route to give the drug, so looking at the safety and the scheduling of the agent.  But in all these trials, the bottom line is can we make the patient’s tumor shrink?  Can we make patients live longer with a better quality of life?

Once a drug is determined to be safe and we have a good idea of the schedule on which it should be given, then the drug moves into a Phase II trial, and this tends to be a much more uniform group of patients.  A Phase II trial will be 40 to 60 patients all with the same type of breast cancer, all the same type of colon cancer or lung cancer, based on where we think the drug might work.

And then if the drug looks sufficiently active, if we see a certain number of tumors shrink, if we get a feeling that the drug might work, then the drug moves into Phase III studies.  And Phase III studies are when you begin to add these drugs to standard of care regimens.  So you’ve got a good standard of care therapy and then half the patients will get the new drug in addition, and half the patients will just get the standard of care treatment.  And the comparison in that Phase III trial is what usually leads to FDA approval and the drugs becoming available to patients throughout the country.

Q: So the Phase III trial is really where the patient is getting randomized, right, and that’s something that concerns patients.

A: It does concern patients.  It’s interesting, when you start to think about it and you think Phase I really early, really new, do I want to participate.  But as you suggest, in a Phase I trial, everybody’s getting the study medication, so there’s no randomization, there’s no placebo; everybody gets the real drug.  When we go to Phase II, it tends to be the same thing.  Now it’s a much more uniform group of patients, but everybody is getting the drug and everybody is getting it on the same schedule, and the patients look much more similar.

Phase III means that the drug has looked active enough and has looked safe enough that now we want to see if it will add to or be better than standard of care.  So now the drug’s been through four or five years of clinical development, but now it becomes the part that you can get a little scary with.  You might not get the new therapy in the randomization, often left up to a computer.

So…and that’s the place where sometimes the placebo comes into play, so a sugar pill or a dummy injection, and that’s a situation where you just have to remember everybody is getting standard of care.  This is what you would have gotten off trial.  And then half the patients are going to get the new medicine and half the patients are not.

Q: One question I often get is in a Phase III trial, well, why can’t I just get the experimental treatment?  Why do I have to  participate in a Phase III trial?

A: And I think that we’ve learned through the years that sometimes we get surprised in a Phase III trial.  So we’ve done the best work we can in Phase I, II to decide what’s the best dose, what’s the best schedule for the drug to be delivered on, and how we should give it to patients, and then we get an idea of how well it works.

And then we go to a Phase III trial where now hundreds or maybe even thousands of patients will be treated, and we will look at it, and you looked at a body of a thousand patients, you might find out that four or 5% of the time you’re having a side effect that isn’t seen in the other group.  So relatively low percentages of events, but enough that it might be a concern once these drugs are out there.

You have to remember, for example, that you’re going to have almost 200,000 women diagnosed with breast cancer in the United States this year, so when a new therapy comes out for breast cancer, the numbers aren’t going to affect, you know, 40 patients or 60 patients like the Phase II trial, it’s going to affect thousands of patients.  And it’s only in those larger trials where we really see the relative benefits and the relative risks for taking the new therapy.

Q: Well, Skip, thank you for your time today, and we really look forward to having you back.

A: Thank you.

[End of recording.]

Q: Welcome to Understanding Cancer.  Today we’re visiting with Dr. Skip Burris, who is the director of drug development at the Sarah Cannon Research Institute in Nashville, Tennessee.  Dr. Burris has extensive experience in new drug development as well as clinical trials in general, with a focus on oncology.  Welcome.

A: Thank you.

Q: I’d like to start our discussion today, which is going to focus on clinical trials, by expressing sort of a common concern that patients have when they hear the term clinical trials.  I think it tends to evoke a little fear.  They don’t want to be experimented on, they don’t want to be a guinea pig.  So when a patient comes in and talks to you, how do you explain what a clinical trial is in your initial discussions?

A: I think that’s an excellent point.  I think you’ve got to take the fear factor away from clinical trials, so we look to several different aspects to it.  And one is that the field of oncology, the practice of cancer cure, has progressed to the point that now participating in a clinical trial is really of standard of care plus.  So you’re going to get whatever your doctor thinks is the best treatment for you, and then you’re going to possibly get something additional that might improve your outcome or might improve how well you tolerate the treatment.

The second part of it is, is really the understanding, the scrutiny under which the trials go, so really quite a lot of look-sees by institutional review boards and by oversight panels, and a lot of thought that goes into designing a clinical trial.  And then, and really, then, the last part about a clinical trial that I think is important is to know that there’s a lot of time, energy and money invested in these, so in fact there’s a lot of motivation to only bring forth a trial that’s got promise to it, so there’s a lot of motivational factors for all parties involved.

The other part about a clinical trial that I think is important for a patient to understand is it gives you an extra set of eyes.  It’s that research nurse, the other components of the research staff that help look over your care.  So actually you end up getting the standard treatment personnel that are helping with your care plus a little bit more in that direction as well.

Q: So in essence, for patients that participate in clinical trials, they could actually be getting more oversight and more care than if they were seeing their regular doctor?

A: Exactly.  And I think that’s the hard part some doctors struggle explaining, ‘cause it’s that feeling that we provide good care already, so what extra could be given?  But the fact of the matter remains that having an extra set of eyes, having somebody else double checking on your test results, somebody else questioning you about side effects or some of the symptoms you might be experiencing only adds to your overall benefit from participating, and I think that in general it’s been shown to improve the care of the patient.

It’s interesting, the NCCN Guidelines.  So NCCN, standing for the National Comprehensive Cancer Network, is a group of cancer centers that publishes parameters, guidelines for what are suggested treatment recommendations for patients with a variety of cancers, and on every page in their documentation they state that the best care for a cancer patient should be consideration for participation in a clinical trial.  And I think that’s an important thing that we try to practice by in our motto at Sarah Cannon Research Institute, is always consider a clinical trial.  That’s often the best alternative for a patient.

Q: You mentioned the institutional review board as one safeguard for patients that are participating in trials.  Are there any other safeguards?  I mean how does a patient know that a trial has been designed with their safety interests in mind?

A: So that’s a key thing for a patient to think through.  They should be presented with a consent form, so this should be a several page document that’s really written in very straightforward language, really try to keep it at a high school education level or below, where it explains the clinical study, what sort of tests you’ll be undergoing, what sort of visits you’ll be expected to make to the clinic, and then get into some of the details about what side effects you might experience.

So that document should, in fact, clearly state that the protocol’s been reviewed and that the protocol’s been approved by an institutional review board.  And on that paperwork you should actually be signing that you’ve read the document and there should be a witness to your signature.  You should also have contact information in that form, so you should be seeing in there that you’ve got a phone number to call if you’ve got a question or a concern.

In addition to the institutional review board, the other part that should come out in that consent form is the fact that the trial’s been reviewed and that there are – if any findings come out about the study or new treatment options become available, that should be made clear to the patient.  When we put a study through the process – also most studies, in fact, will require the FDA to render either a number of oversight to an investigational new drug, for example if a new therapy is being studied, or to exempt it if we know that there’s sufficient information about that investigational new drug.

Q: I always think of oncology as being essentially developmental in nature.  In other words, even when we have a standard of care, there’s still room for improvement, and hence, I’m guessing that’s the recommendation that the NCCN makes, why patients should consider a clinical trial.  Do you think that all patients should actually, you know, have a discussion with your doctor about whether a clinical trial is right for them?

A: I think so.  You bring up a good point about where we are on oncology or cancer care, and it’s really in its infancy.  You know, we’re 50 years out from the very first chemotherapy drugs being delivered.  That’s the nitrogen mustard and some of the compounds, post World War II.  But in fact of matter, really cancer care has been a product of the late ‘70s, early ‘80s, so we’re very early in understanding how to treat these cancers.

There’s probably rare malignancies – Hodgkin’s disease, testicular cancer – where we have very high cure rates, but I would say outside of those two specific examples, a patient should ask about clinical trials.  I think it challenges the physician to really think about what might be best available for the patient, and often it brings up the idea of a second opinion, somebody else taking a look at your case and considering what the most appropriate treatment alternatives might be.

Q: And for the average patient, where are clinical trials typically going to be available?

A: So clinical trials are becoming more and more available in the community setting.  And what I mean by that is we traditionally think about universities or academic medical centers providing clinical trials.  But now the pharmaceutical companies, the research groups all understand that patient care is often best provided in their own community, seeing that medical oncologist or seeing the radiation oncologist who made their diagnosis and has started their initial treatment planning for them, so more and more of these clinical trials are set up in such a way that the patients can receive those therapies close to home.

That’s been a model of the Sarah [Cancer] Cancer Research Institute, to in fact have our clinical trials out there available in these communities.  And I think the doctor that the patient’s seeing is more than likely has access to a clinical trial or knows of a clinical trial the patient can participate in.  There’s also been a growing impetus by the National Cancer Institute to provide, through a Internet mechanism, for doctors to be able to look up on the web site what clinical trials are available, and actually very easy for some doctors to participate in clinical trials on a one off basis participating in that particular study.

Q: It seems, whether it’s the federal government funding the cooperative groups, major universities doing outreach, or organizations such as your own building networks within the community in general, that trials are increasingly more available and part of the overall care plan for patients.

A: Yes, I think that it’s disappointing when you look at the number of patients that go on trial.  We consider ourselves to do very well in terms of accrual of the studies, and even at our center, we’re probably at seven or eight percent of patients, not even reaching the 10% parameter.  Unfortunately, across the country the number is still less than 5% of patients that participate.  And we talked earlier about the advantages of participating in a study, but really moving the whole science forward, and really getting some of these new therapies available for all patients, these clinical trials need to get conducted.

Q: So in my lifetime in oncology, the number of patients that participate in trials, despite a lot of effort by the government and other organizations, hasn’t really increased that much.  What do you think the major barriers are as to why patients don’t participate in a clinical trial more often?

A: It’s interesting that when you look at, in our practice, why patients don’t participate, we still have a large number of patients that the trial is never offered to them.  The physician’s busy or the treatment course seems to be predetermined, that it seems to be a very straightforward approach.  And sometimes it takes an extra few minutes to make that decision and to look things up.  The patient might seem uncomfortable with that diagnosis.

Being told you have cancer is a scary proposition of itself, so to stop at that point and really think about participating in a trial often gets overlooked, and it just simply doesn’t happen.  The other problem is having a clinical trial for your particular scenario of cancer, your stage of cancer or your type of cancer.  So I think have a well rounded menu – we actually try to have a clinical trial menu out there for our physicians so that more likely than not, there is a trial available for that patient.

Q: Is cost a barrier?

A: Cost is a barrier.  I think it shouldn’t be.  I think it’s a perception of cost that’s a barrier.  I think many patients are concerned about their insurance companies and about paying for clinical trials.  I think that’s something that within the study budget, if it’s something outside standard of care, then in fact the pharmaceutical companies are going to be paying or the research funds are provided to pay for those costs.

The other part is in fact many insurance companies, and certainly Medicare leading the way as a government insurance agency, actually advocates participating in a clinical trial.  So taking time to think through that, see what those costs really are, it can often be cheaper for a patient to participate in a clinical trial and have some of their therapies or some of their tests provided.

Q: But to sort through that and those – and other issues, you really have to be seen in a clinic that at least has an interest in wanting to offer patients clinical trials.

A: Yes, and I think, you know, disappointingly so, there is still not a sufficient number of medical oncologists out there that are interested in clinical trials.  It can slow down the day.  It can require an extra visit by a patient.  But I really think that time and that extra visit’s all worthwhile.  I talk to patients about, you know, cancer treatment decisions being urgent, not emergent.  There’s often very little that has to be done that day.

And in fact waiting a few days or a week or two to get the right treatment is better than getting the treatment that afternoon or the next day.  So I think a word of caution about taking a step back, really looking at treatment alternatives, ‘cause really, once you start the process of that treatment, you don’t want to change, so you’re on a treatment course that’s going to go for many months, and prior to taking that first treatment, really think about what your alternatives are.

Q: So clinical trials are something that patients really need to think about as part of their initial treatment planning?

A: They should.  I think it’s always worth asking.  You know, new treatments come along every day.  Drugs move quickly along the development pathway, so they move from very investigational trials to later stage studies where they’re being compared with standard of care.  So really the advances in cancer treatment are moving so quickly that it’s hard for anybody to keep up, any one medical oncologist or any one institution.  That’s why the Internet can be very helpful for patients that have access to that, or really speaking to the nurses or the staff in the clinic to ask those questions and to seek out some guidance in that direction is very, very useful.

Q: I know that when I see a new cancer patient or talk to someone that’s seeking a referral, I typically recommend they get a second opinion, usually at someplace where they have a dedicated interest in their situation.  So if they have colon cancer I typically send them to someone that is fundamentally interested in doing colon cancer research.

A: And I think that’s useful.  I think, you know, a second opinion is nothing for a doctor or a patient to be concerned about.  I think it’s something that we all should advocate more strongly.  Getting a second look at the case sometimes brings out some new features that one hasn’t thought about.  And the fact of the matter is in most times and most situations, the two physicians are going to come close to agreeing.  And patients, in general, are going to want their care closest to home, want it done in the best fashion possible with the most up-do-date treatment, but also where they’ve got the love and support of family and friends.  It’s certainly much easier, socioeconomically, to be treated close to home.

Q: Yeah, I tell patients that they can usually expect one of two outcomes from a second opinion: either reassurance with what your initial treatment plan has been, or you may learn something that could be useful at this point in your care or somewhere down the road.

A: Exactly.

Q: Now, one thing I think that confuses patients is there are several phases of clinical trials.  You hear about Phase I, Phase II, Phase III, Phase IV clinical trials.  Could you sort of concisely walk us through the difference between Phase I, II and III clinical trial?

A: So a Phase I trial is essentially for patients whose tumors have not responded to standard therapy.  So these patients have been through traditional treatment and their tumors haven’t shrunk or gone away.  So their doctor considers them an appropriate candidate, and they’re motivated to look at additional treatment.

So these are brand new drugs, different mechanisms of killing cancer cells, and the purpose of the trial is to really, to look at what’s the safest route and what’s the most efficacious route to give the drug, so looking at the safety and the scheduling of the agent.  But in all these trials, the bottom line is can we make the patient’s tumor shrink?  Can we make patients live longer with a better quality of life?

Once a drug is determined to be safe and we have a good idea of the schedule on which it should be given, then the drug moves into a Phase II trial, and this tends to be a much more uniform group of patients.  A Phase II trial will be 40 to 60 patients all with the same type of breast cancer, all the same type of colon cancer or lung cancer, based on where we think the drug might work.

And then if the drug looks sufficiently active, if we see a certain number of tumors shrink, if we get a feeling that the drug might work, then the drug moves into Phase III studies.  And Phase III studies are when you begin to add these drugs to standard of care regimens.  So you’ve got a good standard of care therapy and then half the patients will get the new drug in addition, and half the patients will just get the standard of care treatment.  And the comparison in that Phase III trial is what usually leads to FDA approval and the drugs becoming available to patients throughout the country.

Q: So the Phase III trial is really where the patient is getting randomized, right, and that’s something that concerns patients.

A: It does concern patients.  It’s interesting, when you start to think about it and you think Phase I really early, really new, do I want to participate.  But as you suggest, in a Phase I trial, everybody’s getting the study medication, so there’s no randomization, there’s no placebo; everybody gets the real drug.  When we go to Phase II, it tends to be the same thing.  Now it’s a much more uniform group of patients, but everybody is getting the drug and everybody is getting it on the same schedule, and the patients look much more similar.

Phase III means that the drug has looked active enough and has looked safe enough that now we want to see if it will add to or be better than standard of care.  So now the drug’s been through four or five years of clinical development, but now it becomes the part that you can get a little scary with.  You might not get the new therapy in the randomization, often left up to a computer.  So…and that’s the place where sometimes the placebo comes into play, so a sugar pill or a dummy injection, and that’s a situation where you just have to remember everybody is getting standard of care.  This is what you would have gotten off trial.  And then half the patients are going to get the new medicine and half the patients are not.

Q: One question I often get is in a Phase III trial, well, why can’t I just get the experimental treatment?  Why do I have to  participate in a Phase III trial?

A: And I think that we’ve learned through the years that sometimes we get surprised in a Phase III trial.  So we’ve done the best work we can in Phase I, II to decide what’s the best dose, what’s the best schedule for the drug to be delivered on, and how we should give it to patients, and then we get an idea of how well it works.  And then we go to a Phase III trial where now hundreds or maybe even thousands of patients will be treated, and we will look at it, and you looked at a body of a thousand patients, you might find out that four or 5% of the time you’re having a side effect that isn’t seen in the other group.  So relatively low percentages of events, but enough that it might be a concern once these drugs are out there.

You have to remember, for example, that you’re going to have almost 200,000 women diagnosed with breast cancer in the United States this year, so when a new therapy comes out for breast cancer, the numbers aren’t going to affect, you know, 40 patients or 60 patients like the Phase II trial, it’s going to affect thousands of patients.  And it’s only in those larger trials where we really see the relative benefits and the relative risks for taking the new therapy.

Q: I want to finish up here with one final question, and that is, if you were hypothetically talking to a new patient and wanted to advise them about how to think about clinical trials, what would your advice be?

A: So my advice for a patient looking at a clinical trial is to get all the information they can.  I try to explain to them what the rationale is behind the new therapy, why we might be looking at this drug, why we might be looking at this new type of treatment approach, and then I have the nurses go through it with them in great detail, look at the consent form and really discuss what the potential side effects might be, and what the potential additional burdens will be for participating in the study, extra clinic visits or extra tests that are [participated].

But I really encourage the patient to strongly consider it.  I do believe that this is the way forward to help not only themselves, but other patients.  The idea that you’re going to have the extra set of eyes, that you’ve got extra staff participating in your care can only be beneficial for the patient.  And we tend to find out sooner if there’s good news or bad news, and we tend to find out about test results in such a way that we can really help the patient’s overall cancer treatment.

Q: Is there anyone that shouldn’t consider participating in a clinical trial?

A: I think that – and that’s where family members can help out – I think really if you’re in a situation where the patient’s in a socioeconomic situation where getting back and forth to the clinic for maybe additional tests or additional visits, that might be a concern.  You know, patients that have co-morbid conditions, so I’m talking about patients with other medical problems, where they’re taking other medicines for diabetes or heart diseases.

I think they need to be very honest with their physician about what’s going on with their other medical problems, and in those scenarios, you know, sometimes that’s a situation where the burden for the patient might be a little bit more than they can handle.  But I think in general the vast majority of patients should really strongly consider talking to their doctor about it and participating if an appropriate trial is available.

Q: Okay.  Well, Skip, thank you for your time today, and we really look forward to having you back.

A: Thank you.

[End of recording.]