The Truth About Cancer
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The Truth About Cancer + Take One Step: A Conversation About Cancer with Linda Ellerbee  

Interview: Dr. David Ryan
< Interviews with Experts

George Demetri

Dr. David Ryan is clinical director of the Tucker Gosnell Center for Gastrointestinal Cancers at Massachusetts General Hospital. He is also Assistant Professor of Medicine at Harvard Medical School.

Interview Content

Misconceptions of "Fighting" Cancer

GARMON: Why did you say the Lance Armstrong kind of culture is speeding into this? I mean what did you mean exactly?

RYAN: Well, I think that you know he has done a lot of good for a lot of different people for a lot of different reasons, but his name now is associated with if I'm strong enough, and if I fight hard enough, and I'm smart enough, and I throw enough money at it, which is the American way, I'm going to beat it. So when people—when you tell people that they have metastatic pancreatic cancer their first reaction is okay, Dave, I'm smart enough, I'm strong enough, I'm going to throw enough money at this and I'm going to go wherever it takes to beat this. Let's beat it. You are just going to point me in the right direction or give me the right drugs and we'll beat it. And they don't understand that Lance Armstrong you know won the lottery essentially. He had the world's most sensitive cancer to chemotherapy that we know, testicular cancer. And his melted like butter. It had nothing to do with the fact that he was an Olympic athlete or this world-class athlete who—it helped to maybe deal with the chemotherapy, but he would have been just as dead as anybody else if his cancer wasn't sensitive to the chemotherapy. I think he probably understands it. I don't know him from a hole in the wall, but people don't understand that. They just see this incredible athlete with an incredible amount of vim and vigor and they think well I can apply the same thing and isn't this great and wonderful and everybody is wearing the bracelet. So when they get cancer the expectation is okay here we go. It's awful because the people who wind up dying somehow, sometimes think that they didn't fight hard enough or weren't strong enough, or they didn't have enough money. I always have to kind of not laugh but chuckle because here you are in—we are in Boston with the world's greatest hospitals. We have some of the world's greatest scientists and I have people traveling to Mexico or San Diego so that they can travel over the border to get something that's going to cure them or someplace else to go where they think that they can get cured. Yet everything, the best that money can buy, in the richest country at the richest time, in the history of the world is right here in Boston but they are going to Mexico or they are going to Europe for some experimental treatment or somewhere. So it's very—there is a certain amount of denial that goes with it I think.

GARMON: I did some volunteer work on the International Mesothelioma program and you know one of the biggest secrets in the oncology community is how unbelievably treatable Lance Armstrong's cancer was. You know what, the public doesn't know that and he raises money on this and he rides his bike on and everything. He goes, but—he said exactly what you said. This cancer just melted away and everyone thought he was on death's doorstep and he wasn't, you know.

RYAN: Well, it's very American to think that you can control your destiny. And in the business world and in the sports world there is something to that. You can control your destiny and if you are smart enough and work hard enough chances are in our system, economic system, you are going to make something of yourself. But when it comes to having metastatic lung cancer or pancreatic cancer, it's all biology. If your cancer isn't sensitive to the chemotherapy or if it's not slow growing, you know, forget about it. Lance, here he literally won the lottery. I mean he did. He was better than the lottery because he lived. You know, the lottery you get a lot of money, but you can still screw up your life. He lived. So it was the lottery for him and you want to say that to patients but then they immediately, if you start going down that road with them, they immediately think that you are a—you are not in it with them. You are not fighting the good fight with them. So it's a very fine line that you walk.

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What is Cancer & Why It Kills

GARMON: So just a basic question. What is cancer?

RYAN: Cancer is a cell that is growing out of control and can go anywhere and invade anything essentially.

GARMON: Why can you die from cancer?

RYAN: You can die from cancer because it interrupts a function of your body that is necessary. Typically the way most patients die from cancer, say solid cancers as opposed to leukemias, it fills up an organ. It fills up the liver, it fills up the lungs, it fills up the brain or hits the brain at a very important spot, the breathing center or something like that. Or it causes people to have blood clots and their lungs can't function when they have a lot of blood clots or the heart stops. So an organ stops functioning is essentially how people die.

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Pancreatic Cancer: Jamie's Experience

GARMON: And tell me a little bit about what you feel you can talk about her case, tell me a little bit about Jaime.

RYAN: So Jaime was very interesting. She actually had a very early cancer several years ago of the pancreas that was caught. It probably arose in a different way than most pancreatic cancers arise in a cystic—what's called a cystic neoplasm of the pancreas and it was resected successfully, very, very early stage, but she probably had some underlying predisposition to develop cancer and then developed another one this past year and unfortunately it was metastatic at the time of presentation. So it was incurable from the start when I met her. We have tried—we tried a clinical trial at first that included the standard chemotherapy plus several of the newer targeted therapies for cancer in general. And for pancreatic cancer specifically we were trying those targeted therapies out. The so-called, smart drugs. It didn't work. It actually worked for a little while. She had a nice response. She clinically felt better. Everything looked better and then her scans came back and we just caught it as it was starting to break though that chemotherapy. So there was a little bit of a disconnect because she was saying, okay I'm feeling better, the chemo must be working and it was. I think it had been working and then it just started to break through. The cancer found a way to be resistant to that chemotherapy. So then we tried a standard second line chemotherapy for people with refractory gastrointestinal cancers and the drug has been around for a long time. It's called 5-FU and she did it. She tried the chemotherapy but it just didn't work at all. The liver metastases clearly became bigger and worse and now she is thinking about whether or not to try a clinical trial in terms of trying to slow this cancer down, but a clinical trial that is one of the new drugs or a combination of new drugs, try another standard type of chemotherapy. Although, I'm less inclined to recommend that because the likelihood of responding to standard chemotherapy if you have pancreatic cancer is extremely low. Or do supportive care alone with the help of home hospice and our palliative care team and hope that the cancer slows down and goes into a quiet period for some amount of time so she gets some good time. And that's where she is currently, trying to make that decision.

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Choosing Chemotherapy, Clinical Trials, or Palliative Care

GARMON: What do you recommend among the 3 choices of conventional chemo, a phase I trial, or pain and palliative care?

RYAN: I think it—well I usually give people the option of all 3. I sit down and try and present it as fairly as I can. My bias as someone who has dedicated their academic life or dedicated their professional life to academic medicine is to find newer, better drugs and my bias is always that people will go on these clinical trials in general. But for each individual patient it may not be the right thing. For her, she feels well, generally, and she is incredibly healthy otherwise so the decision really is up to her and she is a great candidate for a clinical trial of a new drug, a phase I study. But it's really up to her. It's her time. It's limited, we don't know how limited, but we know it's limited and she can decide how she wants to spend that time.

GARMON: What would you—

RYAN: What would I do?

GARMON: If you found yourself in the same situation?

RYAN: Well, it depends. It—I mean it's one of the questions that driving home at night I will often ask myself and I'll think about. I'm a clinician and I'm not a basic scientist. So I don't drive home at night thinking about, you know, this pathway or that pathway that I can toggle with one of these new drugs. I actually drive home at night thinking about, you know, this bad or good interaction that I had with a patient or what would I do in that person's situation. So I actually don't know what I would do because some nights I drive home and I say, you know if I had pancreatic cancer and it's metastatic, I might try a treatment or two, but I have four kids, they are 13, 11, 9, and 6 and the most important thing to me in my life is my kids and if I had a limited amount of time left I would want to spend time helping my kids deal with my illness and try in some way make them feel like they haven't been cheated and prepare them for what was coming next. I think the last thing I would want to do is spend time away from them that wasn't going to be effective time anyway. Then there is some nights you drive home and you say, well if there is something that might get me some more time with them, I would give that a try. The problem with these phase I trials is that we absolutely have no idea what each individual patient is going to get out of that study. We have no real efficacy data really. The paradox between doing these clinical trials or paradox might not be the right word. The confusion that is often felt between the doctor and the patient is that the primary objective of these studies is to find out whether or not they are tolerated and to find the right dose and the right schedule. It's a secondary objective to see if it works. When they ever read the study, sometimes patients ask to read the study and we give it to them and they see that the primary objective is not to make the cancer better it's a whole realization to them that maybe I'm going to rethink what I'm doing. On the other hand, no good drug that we have today wasn't a phase I study at some point, so what you are really doing is trying to see if you can latch on to that next great drug. But you have no idea whether the drug you are trying is going to be that one.

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The Realities of Clinical Trials

GARMON: Your chance of getting on a phase I that's actually going to be an effective drug for your genetic composition of your cancer, it just seems so slim.

RYAN: It is, but it's not zero and we know this because some of the drugs make it. It might be low, but I used to have a slide that I showed doctors, oncologists, when we were teaching them about colon cancer. And the slide was how many people are cured with 5-FU, this little drug that Jaime tried. And everybody would say, well nobody I think, but they would have one experience of someone having a homerun response and it turns out that a fellow at the Mayo Clinic put together the Mayo Clinic and their—what's called the North Central—North Cancer Central Treatment Group, the NCCTG, their cooperative group put together their experience of 5-FU in the old era in the 70's and the 80's and it turns out that about a half a percent of people lived to 10 years and this was with metastatic colon cancer and were felt to be cured. And people who hadn't undergone a resection of their colon cancer. So we know now that resecting these colon cancers, even if they spread, can cure some patients. But these are people who hadn't had any of that and just had the drug. There are these people out there who will have these incredible responses sometimes to these drugs and so you just don't know and it is like a lottery. So if the chance is 1 out of 200, in that setting, and say the chances of having a home run response are 1 our of 200 for a phase I study just to put some numbers to it. People have tried and the number is somewhere between half and 1 percent. People have tried to put that number—and how you define home run can be different. But say defining homerun in this situation is getting an extra 6 months. How many people go out and play Lotto or play Powerball when the odds are 1 in 500 million? Think about what's at stake here. People want to live and when they get in the situation some people will do almost anything to live. Sometimes your job is to hold them back and say that's going to hurt you. You can't do that. That's puts you in a very difficult spot as someone who is doing the research and yet is also the primary doctor for that patient and the primary oncologist. So there is this struggle that you go through sometimes internally about whether this patient really ought to be doing this phase I trial or not.

GARMON: Well, I think you are an incredible team. You were incredibly honest with Jaime about the phase I trials that she might be in line for and I thought—I couldn't imagine ever witnessing an academic doctor push so little for a phase I trial as you. I mean you seem to try to be—I'd have to go back and look at that footage now, but you seem to be trying to talk her out of it.

RYAN: Well, it's not so much talking her out of it. It's I want her to appreciate what she is getting into. And I think that there is a misconception out there that we as oncologists, and particularly academic oncologists, all we care about is our research. And all we care about is the particular drug that we are studying right now and the patient is secondary, the patient is a subject. And that couldn't be farther from the truth. I mean that's the last reason I'm doing what I'm doing right now. The patient is everything and I know I have this bias to find new drugs. So I want to present the options to her as fairly as I possibly can. Unfortunately I think sometimes my own personal style can be a little blunt and I worry about that. But on the other hand, I also worry that this is her time to spend as she chooses to spend it and I'm willing to give her more chemotherapy and do a phase I study if that's what she wants to do. But I'm also very willing to support her as best I can if she says to me, Dave, look I want to go to Europe, and then I want to go to Hawaii, and then I want to take my nieces and nephews to Long Island to go fishing. And if she says to me that's what she wants to do, I'm in her court 1000% and I want her to know that because she is getting mixed messages from all over the place and the cultural message she is getting right now is fight, fight, fight. Chemo, chemo, chemo. So it's very easy for me to say I've got a new drug for you. In fact, that's the easiest thing. To walk in a patient's room who is in her situation and go I've got a new drug for you. That is the easiest thing I could have done. But is that the fairest thing for her? And am I fulfilling my responsibility as her physician because you know first and foremost I am her doc. You know, I have got to look out for her.

GARMON: So as an academic doctor though, don't you also have a responsibility to enroll people in trials? We have heard today that only 4% of all the patients in the United States enroll in clinical trials. I mean enrollment is so low. Are you ever concerned about that?

RYAN: Absolutely, but that's the culture. That's the culture of control that we live in where people want to control exactly what they are doing and they have this big fear that if they go on a clinical trial they somehow loose some of that control. I'm not going to fix that by sacrificing my principles as a physician to treat this person as kindly and compassionately as I possibly can. I mean, first and foremost, it's me and the patient always. And the drug, or the trial, or the company, or the NCI, you know, they can jump in a lake. It's me and the patient.

It's not that I don't believe in them. In fact, if you go back to the records I'm probably in the top 5 in Boston for enrolling patients in phase I studies in terms of the numbers of patients put on phase I studies. In fact, my unit the—I run the GI cancer center. My unit enrolls more people on phase I studies than any unit in Boston.

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A Phase III Clinical Trial

GARMON: Actually about my favorite trial example, this is a phase III study, was there any home run on this lovely trial?

RYAN: Gemcitabine plus Erlotonib, that's the—or Tarceva. That is the targeted smart drug. It targets the epidermal growth factor receptor. No, if you say this is a home run you are kidding yourself. So the way I describe this to patients is it's a bunt single. It's a bunt single. Now what's interesting about this drug is that—or this trial is that there was a little bit of a tail on the curve in the sense that our experience with clinical drug development, more often than not, is by little and little and you build on each little improvement. So what Erlotonib taught us—what's interesting about this is if you got the rash, your chances of living for a year were actually pretty good, unlike if you didn't get the rash. So the real key for this particular study and the real failure right now in academic oncology to a large degree is there is a certain small percentage of patients that might benefit from this particular drug, we don't know who they are yet. Now we have done that in lung cancer. So there has been some breakthrough recently. Recently there has been some breakthrough where we are identifying those specific patient populations that will benefit. It's small, but it's real. So in lung cancer it's somewhere in the 5% to 10%.

GARMON: So are we talking about Tarceva?

RYAN: Yes, so that's—yes Erlotonib is Tarceva. So I have seen people on Gemcitabine and Erlotonib or Tarceva who had these great responses. Whether it was due to the Gemcitabine or the Erlotonib, I don't know, but there is something going on. So what I would characterize that study is it's a signal. It's a signal that for a small percentage of patients, there is something good going on and that's better than everything else that we have seen in pancreatic cancer in the last 10 years. So that's part of the reason why there was excitement about that. But it's not a home run. I mean it's a bunt single at best.

GARMON: Because the median difference was 0.47 months.

RYAN: Correct or as we like to tell people, 2 to 3 weeks. That's the median.

GARMON: But, as you say, what's missing in this sort of trial is a proof of concept. What's missing in this trial is we are going to launch this trial, but the patient population we are going to enroll—we are going to show some evidence before we enroll them that they might benefit from this the most.

RYAN: But yes and no. So they did prove their concept that they saw a signal. What they didn't do—the failure in this particular study is you can't—you don't know which of the patients that aren't going to benefit. But for example, this is pancreatic cancer where we are just hopefully starting to take baby steps. In colon cancer, when I just started 10 years ago, the median survival without chemo was about 6 to 8 months. With chemo it added 3 to 4 months. So you got about a year. Then all of a sudden we had one drug and it added 3 more months. And then we had another drug and it added 3 more months. Then we had another drug and it added a couple more months and now we have another drug and it adds a couple more months. So the median survival with colon cancer in 10 years has gone from a year with the one drug that you had to about 2 years now. Now if you look at each one of those individual steps alone you can always say well that is awful. What's a 2 to 3 month improvement in survival? That's awful, but when you add them together what we have seen in colon cancer we saw it in breast cancer and we are seeing it in colon cancer now, and that's the median. So that means that now I have a clinic full of patients who are alive 3 and 4 years because they responded to the chemotherapy and they have colon cancer. I still have patients who are completely resistant to the chemotherapy and they die within 6 to 12 months. But it gets back to the original point which is it's all about the biology. You are either sensitive to the drugs or you are not. So the excitement over that study isn't that—nobody can with a straight face say that that's a home run even though the drug company does, but that's what they are in the business of doing. But it was at least we took a baby step. You know, we fell down right after we took that baby step, but as somebody who has tried to take baby steps for people with pancreatic cancer for the last 10 years, believe me at this point I will take anything in terms of any movement forward. So this is just a little tiny glimmer of hope and what I'm hopeful for is that 10 years from now when I sit down with somebody—just like 10 years ago when I sat down with my first patients with colon cancer and all they had was 6 to 12 months of median survival and now they have 2 years and I have a few people, 20% now are living for 5 years in some of the studies. I mean that's 20%. So that means you have got metastatic colon cancer and a 1 out of 5 chance of being alive 5 years from now because of the chemotherapy. Well 10 years ago it was 5%. So that's progress. What I'm hoping is 10 years from now I'm sitting down with someone with pancreatic cancer and I could say to them, well you know the median survival now is a year or a year and a half which beats 6 months with Gemcitabine, which is what we have now, or 3 to 4 months without it. So you have to take the long view.

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Ideal Changes to Cancer Care & Research

GARMON: If you were just named magic czar of all of cancer in the United States, what would you change about the system to make research maybe hastened bench to bedside, you know, discoveries. Make things go faster, more productively. There is a frustration out about in the land that things just aren't moving as fast as anyone would like.

RYAN: I think that I would probably have regionalization of care. Particularly for early stage cancers because the cure rate is clearly higher for some of these cancers that are removed by surgeons and institutions that know what they are doing.

GARMON: I don't know what you mean by regionalization of care.

RYAN: So that if you—it's pretty—take the east coast. It's pretty hard to live 3 or 4 hours more—or more than 3 to 4 hours away from a cancer center that offers you outstanding surgeons who know how to take out pancreatic cancer or who know how to take out cancers that have metastasized to the liver or who know how to take out lung cancer, or esophageal cancer, or any of the solid cancers that we have, or know how to treat leukemia expertly. I think that there needs to be some regionalization of care, particularly where it's been proven to be beneficial and yet we have the proof in many of these cancers that going to a center of excellence makes a difference. Maybe not when you have metastatic disease so much, but even that is starting to change a little bit. The second thing I would do is the fact that we are spending so much money on drugs that don't affect survival at all is a travesty. I mean it's a national outrage that we spend more money on drugs like Aranesp and Procrit that up your red blood count. It's never saved a person's life. We spend more money on these anti-medics that yes make life better, but we are spending more money on those drugs than we actually do on drugs that save lives and extend lives significantly? It's outrageous and we haven't devised a good system to reward companies for developing drugs that save lives more than we've developed rewards for companies that, you know, for making Viagra or Aranesp or Procrit or things that are quality of life type drugs, but have no effect on survival and making people live longer.

GARMON: We should probably explain what Procrit—that's like for your red blood cells or— it's been a while since we've been through the Procrit thing. I don't know what Aranesp is?

RYAN: The same thing.

GARMON: Oh, okay. A thing that you would change and you are I guess trying to say you are trying to make incentives in the system for people to do life saving drugs rather than make a ton of money off of it.

RYAN: Correct. Well yes, I think it's a national outrage that we don't have better incentives to make drugs that save lives rather than drugs that just improve the quality of life. Quality of life is such a subjective end point, and most of these drugs, for instance the drugs that boost the red blood cell count like Procrit and Aranesp or the drugs that—do we really need 5 different anti-nausea drugs? Yet we are spending as much money on these drugs, if not more money on these drugs than we are spending on drugs that actually save lives or extend lives at least. And somehow there needs to be an incentive for companies to develop these drugs that really extend life and rather than just make them a boat load of cash because they may—they figured out some quality of life measure like Viagra or any of the white blood cell boosters. Do we need another one? No, we don't need that and we are spending crazy amounts of money in Medicare and insurances to spend money on these drugs that really at the end of the day, have you asked anybody who's had pancreatic cancer, or lung cancer, or breast cancer and was dying of their cancer that boy they were glad that people came out with these drugs even though they didn't make them live any bit longer. No, their big regret is gosh I wish you guys had another good drug for me or another drug that was going to slow me down. When you see a drug that actually works like a Gleevec or Tarceva in lung cancer, all these problems, they go away. You know, the cancer causes the anemia. The cancer causes all of these quality of life issues. When people respond well to the cancer your quality of life dramatically improves.

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Possible Treatment for Jamie: PI3 Kindness Inhibitors

GARMON: Is a PI3 kindness inhibitor a possible with Jaime this fall?

RYAN: Maybe. So the PI3 kindness inhibitors are the hot drug right now in solid tumor. They are the endostatin of a couple of years ago. Let me explain what I mean by that. Judah Folkman is the champion of angiogenesis and antiangiogenesis in the world. His first new drug was this drug called Endostatin and it was supposed to starve the tumor of its blood supply and I was a participant in the phase I study of that. One of the first phase I's that I participated in and I remember when it first came out I was desperate for my patients to get on that because I believed in anti-angiogenesis and I believed in the power of Endostatin and we had so much interest in that drug, national interest, that we actually had to set up a lottery to get on it. So that just because you knew Ted Kennedy it didn't mean that you were going to get the drug. It really was a lottery and we thought that was the fairest thing. And I can remember I was taking care of a 23-year-old at the time who was dying of colon cancer and we had exhausted the standard therapies just like we have done with Jaime and I really wanted her to get it. I remember thinking to myself, you know, gosh I hope she wins the lottery. I hope she wins it. You know, she didn't win the lottery. So she never got it. It turns out there was another drug being developed at the time that was very boring that actually extended survival. So the PI-3 kindness inhibitors, you know, they may be wonderful, they may be a home run, but if you do this long enough there is always a new home run that's out there and I think you have to take the long view. Let's study it. Let's make sure it's safe and tolerable. Let's get through the phase I studies. If it's appropriate for her to go on a PI-3 kindness inhibitor and we have a study available of a PI-3 kindness inhibitor, sure I'm happy to offer it to her. Right now we don't have one available for her to go on.

GARMON: Are you looking at one that would be offered by Novartis?

RYAN: Right, so we are. We do have studies within the system not just one that she is eligible for right now though. So it would have to be open to all people and so hopefully some day we will have some PI-3 kindness inhibitors but we will also have other drugs too. There is M2-R inhibitors and there is novel EGF inhibitors, there is combinations now of M2R and EGF that look very interesting. There is a whole bunch of pathways that people are looking at to throw all your hope into one basket, the PI-3 kindness inhibitor, it's a little much. I'm hopeful it works, but I kind of pick the long view and realized that in medicine it's often the things that you didn't expect that worked and the things that everybody got behind often didn't work and sometimes caused harm.

GARMON: What was that quiet little drug that no one wanted to pick?

RYAN: Oxaliplatin.

GARMON: And that one extended the life more than Endostatin?

RYAN: Oh, yes.


RYAN: And it was a standard cytotoxic old chemotherapy drug that is now first line chemotherapy for people with colon cancer.

GARMON: And would you say that that was a single, a double, a—

RYAN: It was a solid single, if not a double.

GARMON: And what was Endostatin?

RYAN: it was a dud. It was a dud and it didn't work. It was one of the 9 out of 10 drugs that we do in these clinical trials that turn out to have no effect and at worst are harmful.

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The Importance of Hope

GARMON: I remember. I remember. I was on the phone with [Judah Folkman] when my husband was—he said have hope but—

RYAN: And hope is important.

RYAN: Well, I think my hope is in the process. It's not in the individual drug, it's in the process. I really believe that we are making progress and we have seen it in colon cancer, we have seen it in breast cancer. We are seeing it now in lung cancer. I'm really hopeful we are going to see it in pancreatic cancer, but that process is a 5 year long process, a 10 year long process, and it's not the same kind of hope. I don't hope for a cure for pancreatic cancer. I think that's a little bit pie in the sky. What I'm hoping is that we make pancreatic cancer for some patients into a chronic illness. The kind of chronic illness that we have made breast cancer for some patients. The kind of chronic illness that we are making colon cancer for some patients and hopefully making lung cancer for some patients. I'm hopeful that that's what we are going to do for people with pancreatic cancer and the only way to do that is through the process of clinical trials and phase I studies and phase II studies. Maybe the PI-3 kindnesses are it, but maybe they are not. Maybe it's something else that somebody is working on quietly that nobody knows about right now.

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The Business of Clinical Trials

GARMON: I'm not as obsessed as I sound about them, but I heard abut them in the spring when we were launching research and the trial was immanently getting off the ground then. And then it didn't look like it was going to happen this summer and now it doesn't look like it's happening this fall. So what's the delay with this thing? I mean is this typical clinical trial delay?

RYAN: Pretty much. As far as I know. I'm not intimately involved with that drug, but I know about them in general and clinical trials are hard. Remember you have people's lives at stake and you can't just Willy Nilly throw drugs at people. You know, one of the arguments that you will see often and the Wall Street Journal is a big proponent of this, "well why not, they are going to die anyway." You know, that's the big Wall Street Journal line and it's a very kind of libertarian approach. Well if you inform the patient they are dying anyway throw anything at them, why not? Have you ever killed somebody with a drug? Have you ever watched somebody suffer because a drug you gave them made them miserable? Is that the most compassionate thing you can do to somebody sometimes? When you know they are dying and your job is to comfort them, you know. It's very easy to sit at the editorial page and say throw whatever at them if they are informed and these patients are desperate, but it's not easy to watch that and you do enough phase I studies, you do enough clinical trials, you will kill somebody with a drug. They will die. You didn't kill them, but they will die because of your drug and that's a—it's a form of violence. It's very hard to watch people die sometimes particularly from the chemotherapy that you gave them. It's—and I think what makes us recoil is the violence of it. Yet, we know we have to push forward to find better drugs, but I'm under no illusion that because Novartis or somebody else who is worth millions of dollars, billions of dollars, however much they are worth. And believe me, those people who are running Novartis they stand to gain a fortune. So they have their own agenda. I have never met a drug company person who hasn't believed in his or her heart and soul in that particular drug. But they are incentivized to believe. You know, and they also want to believe that they are doing good. But you know what, it's very easy to believe you are doing good when what you are doing is making you or could make you a fortune. So you always have to remember that these people you know they have conflicts of interest, too. It's not just the academic oncologist who have conflicts of interest. So—and you always have to come back—I mean it's your patient. Its your—that's whose life you are responsible for. And when you think of who you want as your doc, you know, you want someone who is looking out for you. You don't want someone who is a cold calculated developed of clinical trial or maybe you do. But that's not the kind of person that I am and that's not the kind of doctor that I hope that I have been. So I get very upset sometimes when I hear that—I see the point of the whole libertarian argument of throw it at them, but there is a down side to throwing drugs at people Willy Nilly.

GARMON: That sounds like it would be a very tough experience. It wouldn't be something I would want to see. I know the Advocate of Alliance for drugs and the Wall Street Journal is behind them and I've read certainly their bias is—but I wouldn't want to be in a position to do it.

RYAN: No, and I think the process we have set up is actually a very good process and people have spent years developing this process. Could we do it better? Absolutely. Are people running out of time who are dying right now? Absolutely. But you know you can't cure the human condition either. I mean people do die and that's not going to change. So you have to do this in a way that it preserves people's dignity. Recognizes that they are in desperate situations and above all do no harm. You know you can't hurt people.

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Where We Are in the War on Cancer

GARMON: So where would you say—without just leaping to the big picture again. Where would you explain to a general audience we are in the war on cancer?

RYAN: I think when somebody says they have cancer you are talking about a hundred different diseases. I mean you may as well say I have heart disease. What is it? Is it atrial fibrillation? Is it heart failure? Is it coronary artery disease? The same thing is true with cancer and there are many, many different types of cancers. Some of them we have hit home runs on. They don't happen to be the common cancers necessarily, but I also think you have to realize that what you define as a home run has to be a little bit different and when you can take somebody with breast cancer and give them a median survival of close to 3 years with the drugs that we have that's a home run. That's 3 years that they otherwise wouldn't have had on average and some of those patients are given 5 to 10 years because of the drugs that we have had. That's a home run for that individual patient. This concept that you are cured, cured of what? You know when you are 70 the average person with cancer in this country is considered elderly. When you are 70 are you going to live forever? No you want to get extra time to spend it with your family or your loved ones or doing what you love to do. So you have to have a better definition of what is and what is not a home run. I think in breast cancer we have hit a home run. In colon cancer we are in the process. I mean we have hit a triple I would say. Particularly as someone who has taken care of people before we had any drugs. We had 5-FU. We are hitting one. Is it a cure? Not for everybody. For some people a small percentage, but for a lot of people they are making graduations, weddings, births, these great life events that they otherwise wouldn't have made.

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Cancer Care Successes

GARMON: What about metastatic lung cancer due to smoking?

RYAN: What about it?

GARMON: Have we hit a home run there?


GARMON: Have we had a single?

RYAN: We extend—we give people some extra time, maybe a bunt single we have hit.

GARMON: And what about prostate cancer, another common cancer?

RYAN: I think with the hormones that have been around people can do well. I think that we are in need of better drugs for people who have hormone refractory prostate cancer. We haven't hit a home run there yet.

GARMON: We haven't hit a home run with African Americans either.

RYAN: We haven't hit a home run with certain populations and why that is, you know, we just don't understand the biology well enough.

GARMON: So for one of the most—for some of the most common cancers, leaving aside the rare ones now, your cancer score card would be what?

RYAN: I think that the biggest disconnect between oncologists, and academic oncologists, and patients is that our definition of a home run is we are getting people extra time. We are making this into hopefully a chronic illness. People expect to be cured and it gets back to that whole discussion of people expect to live to 80 or 85 and even what's been a huge revelation to me in the last several years has been how many people who are 80 come in and want to make 81 and say to you, Dave, give me the chemo. Give it to me. And you are like, well your heart, your kidneys, I'm not so sure. What are you talking about? I want to make 81. It's very hard and it gets back to that whole thing of what's life about and it used to be that when you died and you were in your 80's it was a celebration and of a life well lived. That you made it to 80. And we often joke, I mean, gallows humor among oncologists, but if God said to you tomorrow, I will let you live to 80 and not a day longer, would you take it? Or he says, she says, take your chances. So if God says to you I'll let you live to 80 or take your chances but you won't live a day longer than 80 if you make that choice would you take it?

GARMON: Are you asking me the question?

RYAN: Yes.

GARMON: It would depend on the quality of life. Are you saying I have—

RYAN: You have a good quality of life until 80. You maybe have some basic low—

GARMON: I'll play the game. Yes sure now I would say that, but that's a long way off for me so you know I probably say that now over living longer and having a poor quality of life. But ask me when I'm 79 and I'll give you a different answer.

RYAN: And that's currently what's happening now. So when people get frustrated sometimes their frustration really I think isn't directed at us so much as it's directed at the human condition.

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Why Cancer Doctors Do What They Do

RYAN: Have you asked anybody why they do what they do? Because the biggest question we get a parties is—the biggest question I will get at a party or someplace out is, well, how do you do what you do? How could you do that? I mean it's the biggest—when people find out that you are an oncologist at a cocktail party or something it's the biggest discussion downer and halter that there is. Nobody wants to talk to you after that unless you are at a family function. Then everybody wants to tell you their PSA.

GARMON: What's your answer?

RYAN: How could you not? In the oncology clinic exists the possibility for the best that people have to offer to one another and you get to be witness to that everyday. So it's like you can't make these stories up. It's like living a movie sometimes. And you get to be a part of that and then you get to provide care in a compassionate, kind way. So when you realize you have the opportunity to do that, to just walk away from that is incredibly difficult.

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