Vincent T. DeVita, Jr., MD, and Maurie Markman, MD
Maurie Markman, MD: Hello, and thank you for joining us today for this special program. We’re going to be talking with Dr. Vincent T. DeVita, who has been one of the most influential researchers and physicians in the oncology care arena. Dr. DeVita has received many honors over the years, including a Giants of Cancer Care Award in 2013. He is perhaps best known for helping to usher in the modern era of chemotherapy in the mid-1960s with his development of a 4-drug regimen for the treatment of patients with Hodgkin lymphoma. His colleagues named that discovery one of the top advances in modern oncology in an oncology poll. Now, Dr. DeVita has written a book about his experiences in cancer research and treatment called, The Death of Cancer.
My name is Maurie Markman, and I am the president of Medicine and Science at Cancer Treatment Centers of America and the editor-in-chief of OncologyLive magazine. I’d like to welcome Dr. DeVita and thank him for joining me in this program.
The title of the book, The Death of Cancer, after 50 years on the front lines of medicine, a pioneering oncologist reveals why the war on cancer is winnable, and how we can get there. So, my first question many people would like to know is, why did you write the book?
Vincent T. Devita Jr, MD: You know, the American people paid over $100 billion in taxes for the war on cancer. I was in an unusual position in the sense that I was in the right place at the right time. I was there at the Cancer Institute before the Cancer Act was passed. The work I did was partly responsible for philanthropist Mary Lasker getting interested in cancer. Then, I wound up running the whole program, and then I wound up outside at two major cancer centers. And then, I had the opportunity to be president of the American Cancer Society.
As if I didn’t have enough experience, I got cancer myself. I said to myself, “I should. A person in that position should really recount their experiences, so that people know what they got for their money from somebody who actually saw it happening.” So, I did it, and I did it with my daughter, Elizabeth, who’s a tremendous writer. I said [for her] to keep me honest and to help me translate what I was doing. The book is actually meant for lay people, not for doctors and nurses. Some people think it’s only written for doctors and nurses; it’s not. That is the reason why I wrote it.
Maurie Markman, MD: Now, I certainly appreciate that. In reading it, I absolutely appreciate the fact—I think my wife has read it—that it was written for the lay audience. My question is, “What is the major message you would say that you wanted to leave, and have left, with those who have read the book?
Vincent T. Devita Jr, MD: The major message is what you’ve already mentioned—that the war on cancer not only is winnable, but it is actually being won. People don’t appreciate the significant change in the whole cancer field since the Cancer Act was passed, way back in 1971. The mandate of the war on cancer was to support research, the application of the results of research to reduce the incidence, morbidity, and mortality from cancer. In the Cancer Act itself, there was never any mention of timespan. It didn’t say by the bicentennial. That was Mary Lasker’s little thing to get the Congress moving.
Therefore, since 1971, we have put 65% of the $100 billion into support research—a lot of money in research. The incidence and mortality rates have been coming down since 1990, 1991. It is never easy to be treated with cancer, but the morbidity is way less than it was. If you look at mastectomies, for example, when we were starting out with radical mastectomies in breast cancer, the chest wall was denuded. Again, after radiation, the chest wall would swell up. It didn’t do much because the cells had already gotten out.
Therefore, it was a highly morbid and less effective treatment. Now, we have lumpectomies with radiation therapy, we save the breast, and the mortality from breast cancer has come down 25%. Overall, the national mortality has come down 25%— probably more, now, because these data are 5 years old. When they get to actually measure the 2016 rate, it’s probably going to be more like 35%. It is supposed to be a very steady decline.
So, that is the message: we are not only winning, it but it’s winnable. I mean the latter because I think the new stuff, you know, the targeted therapies, the immunologic therapies, are not even in these data.
Maurie Markman, MD: Right.
Vincent T. Devita Jr, MD: They’re just hitting the clinic, so the best is yet to come. We know they’re going to be good. I think we need an optimistic message to people. One of the reasons people are confused is that, when we treat people with cancer, what we want them to do is go home and live a perfectly normal life, and they do. The great majority of them don’t walk around and say, “I had cancer and I’m....” Some do; some become activists. But, the great majority don’t. The ones you see, generally, are people who are suffering from it, and they’re much more visible. People don’t appreciate how many people are being cured already of their cancer.
Maurie Markman, MD: It’s a very important message and a very positive one. Although it’s very clear that you’ve written it for the lay public, was there or is there, a message also for medical professionals—either oncologists and/or generalists?
Vincent T. Devita Jr, MD: As I point out in the book, there are some doctors who are not enthusiastic about treating patients with cancer. There’s always been this tug of war. You have cancer; it’s a self-fulfilling prophecy. It’s a lethal disease so you don’t treat it. If you don’t treat it, it’s a lethal disease. Some cancer patients get themselves in the hands of doctors who don’t believe. If you’re newly diagnosed with cancer and the doctor says, “you’ve got cancer, there’s nothing I can do for you” you should find another doctor, because there’s something you can do for virtually everybody, nowadays with cancer.
Maurie Markman, MD: It’s such a wonderful book and your daughter is obviously a terrific writer and, obviously, the two of you together just made a wonderful story. Because it is, again, written for the lay public.
Vincent T. Devita Jr, MD: That’s why we did it that way, because she really has a talent for capturing, or getting the color in the story. There are a couple of places in the book—Jay Ferrick telling me to give an antibiotic in a way that, the label says, you don’t do it.
I just told it that way and she said, “Well, where were you?” Well, I was standing on the Two East Floor. “Well, what happened?” I’m standing with Jay, he’s 6-foot 5-inches, looming over me, and he pointed his finger, and then she gets all this color in the story and it brings people into the book.
I think I mentioned to you that I wrote 320,000 words, which would have been a book about three times this size. I handed her the manuscript and she handed it back to me with 110,000 words, the current book— a more readable fashion—and said to me, “No much point in writing a book if people don’t read it.” So, this is much more readable. Without her, I think it would have been a completely different book.
Maurie Markman, MD: Some of the conversations and issues in the book, and one that we absolutely want to mention and discuss, and ask you to comment on is this concept of cure. You make a point in the book of very clearly discussing that cancer is winnable and you advocate talking about cure. Do you want to comment about your thoughts on that?
Vincent T. Devita Jr, MD: Nowadays, I find that the fellows are not encouraged to use the word cure. I’m a little of an outlier at Yale. [It’s] “We don’t know that you’re cured.” It’s very conservative. It’s more like, be a little afraid. If you encourage them that they’re cured and they relapsed, you take the blame for them relapsing.
I think patients would rather be free of cancer. They don’t want to be told that you’re not cured; we can’t be sure you’re cured. They want to go home and feel comfortable. There is a time, almost with every cancer, when you know that if they have not relapsed after treatment, they’re not likely to relapse.
For example, in Hodgkin disease, it turns out to be about 4 years. They go into remission and stay in remission and are off treatment for 4 years. We are doing the 45-year follow-up of our first group of 188 patients, and those patients are cured. They are alive, free of disease and lived a perfectly normal life. My feeling is, you should tell them they’re cured, and give them the optimism for it.
Now, we have very interesting things happening in the cancer field. The best example I know of is chronic myelocytic leukemia where we are treating patients; this is a disease when I started out that was uniformly fatal. We could patients in remission for a few short period of time, but it was uniformly fatal. Now, they take a pill and they live a perfectly normal life. Then, when they develop resistance to the pill, the pharmaceutical industry has developed 4 others that they could take, and probably we will keep doing that. You can always treat the disease, so they aren’t cured. They’re just living a perfectly normal life.
We’re now having a different category of patients who are able to live with their cancer for a normal life, as opposed to those who have no evidence of cancer. I think we’ll see more of that. Using some immunotherapy approaches, I think we’re seeing patients whose cancer just goes into abeyance, but they still have evidence of disease if you look hard enough. It is a new category, so you need to explain that difference to patients. But, when it’s possible to say with some confidence that they’re cured, I like to say, “You know, you’re very likely cured of your disease.”
Maurie Markman, MD: Vincent, in the book, you’re quite open, honest, and eloquent in your description of your own experience with cancer, but also with the experience of your son and his illness. How has that influenced you, your thoughts at the time, but also now for the future?
Vincent T. Devita Jr, MD: Well, my son had anaplastic anemia. He was put into a laminar air flow room to protect him from getting infections. He stayed there for about 8 years. Except for some excursions—we worked with NASA and let him walk out with a spacesuit—he never left that room. I thought that I had a lot of empathy for parents of children who died of leukemia or had leukemia, but it’s a whole different experience to go through it myself. I think it made me a better doctor. It changed me in a whole host of other ways.
My own cancer—I developed prostate cancer—and I think I did what a lot of doctors do. They tend to ignore it and [have a] “do what I say, not what I do” [approach]. I finally was diagnosed—and it was a difficult case, the prostate was very large—I realized that what I normally did for patients, navigate for them and find places for them to get the best therapy, I couldn’t do for myself. I had to ask my colleague, Dr. Steve Rosenberg, to do that for me. He did a great job and steered me to one of the finest surgeons in the country, Dr. Peter Scardino. It gave me an insight into being in the medical system, how difficult I knew it was; but then when you experience it first-hand, it’s a little bit different. It changed me quite a bit.
Maurie Markman, MD: You discuss a number of controversies throughout your career. Starting with the resistance to combination chemotherapy and looking back, why was there so much reluctance to these innovative approaches, which now are standard of care? Today, I certainly see reluctance to novel ideas. There’s so much resistance to doing something new and novel. What are your thoughts on this?
Vincent T. Devita Jr, MD: Well, let’s do it in two parts. The second part I’ll come back to. The first part was in the 1960s. The thought that you could cure cancer with drugs was considered insane, and the doctors who were doing it were, in fact, called insane. The methods were fairly crude. Epithets that were thrown around at Grand Rounds at people who were trying to do this were extraordinary.
I was a young doctor and I came from a university where no one would tolerate people doing that at a university. It was just considered madness. Using drugs in combination was considered bad medicine. Primarily, it stemmed from using antibiotics in combination. They were relatively benign. When you started using toxic anti-cancer drugs in combination when they, in their minds, had no hope of doing anything except making patients sick, it was considered just too far out.
The environment that we did this in was the National Cancer Institute, and it was a somewhat protected environment where we could actually do these things, take some criticism, but nothing stopped you from doing it. You were sort of limited by what was between your ears. It would have been impossible to do it elsewhere. I went to Yale, took some time off to finish my residency, and I tried to implement some of these things at Yale. I was told, in no uncertain terms, that this was nuts, and I turned around and came back to the National Cancer Institute.
Today, I do see the same thing. I see people who still are reluctant to do innovative things. For example, we have proof of principle that we need combinations of different agents to cure cancer. With very few exceptions, you need combinations. In fact, you’re looking at it now in melanoma, where clearly immunotherapy that is combined is better than a single immunologic agent.
I don’t know why we have to keep proving this all over again. But, we’re proving it all over again because the FDA requires us to prove it all over again. I think the FDA is still in the last century and needs to come into this century, and we talk about that quite a bit in the book. I think one of the problems we have is that we are overregulated. Doctors are fearful that if they do something a little off the beaten path, then they will be penalized for it and lose their ability to do research, or be considered not collegial and so on.
Maurie Markman, MD: So, you discuss the concerns. You certainly mentioned the FDA in the book. I guess I would ask you, how could we change the situation? Obviously, I feel some of the frustration. The advances that have occurred are spectacular. The advances that could occur are far greater. Yet we are in an environment, as you described in the book very eloquently, painfully slow. Of course, the FDA and their rules, as again you discuss, go back 60 years. What can we do to fix this?
Vincent T. Devita Jr, MD: One thing I tried to do is write the book. I thought it’s possible we could get the attention of the only people who could really fix this, which would be the Congress. I think what happens today is that doctors don’t realize where they are. They’ve been backed into a situation where the FDA is essentially practicing medicine and directing research. If you look at the handbook on chemotherapy with a certain drug, it will tell you, “this drug has been approved for use after they’ve had this drug, before they’ve had that drug, and at this stage,” and so forth.
This is somebody who is 3000 miles away from the patient telling you exactly when you can use it. Most of the innovative stuff that’s going on is usually done in the after marketing period. The FDA essentially has paralyzed the after-marketing period by doing this. I think there is a simple solution, and I talk about it in the book. The FDA and the National Cancer Institute should delegate all phase I and II clinical trials completely to the cancer centers. The FDA and the NCI could reserve the right to come in and do audits. They have it now, and they could do it then. But, they should delegate all the responsibility. You can start a phase I trial in your cancer center and you don’t have to go back. If you want to make changes, you don’t have to go back to the NCI or the FDA. You can make changes with your own internal review committees, and you can do that for phase II studies where most of the good stuff is happening.
I also think that the FDA should change how it approves drugs. It should approve drugs based on their safety, but safety in the context of the patient that it’s going to be used in. Safety is a different creature when you’re using it for an anti-hypertensive drug that a patient is going to take for the rest of their lives. Safety, and the ability to hit a biologic target, is important.
If you develop a drug, or a receptor you know is important, and it hits that receptor, they should approve it. You put it into the therapeutic armamentarium for the doctors, and the doctors are able to mix and match the way they want to use the drugs. I describe a meeting that, in the early days, we called “The Society of Jabbering Idiots.” It was actually the best meeting I’ve ever been to in my career, because it was essentially a war room where all the data that was going on in the wards, it was matched with the data in the labs and we could make adjustments to the protocol and go right on the ward and do it. Nowadays, it can take 800 days to take those adjustments back through the review system.
You delegate the responsibility for this to the cancer centers, and they could each have their own society of jabbering idiots—excitement, know the biologic pathways and all the mutations, and be able to mix and match therapies.
What’s intriguing about this is that it would not only make things a lot easier, it would cost less. You don’t need an infusion for the moon shot to change this; you just need the FDA and the National Cancer Institute to give up some power and authority. Unfortunately, in Washington, D.C, no institution gives up power and authority voluntarily. So they’re going to have to be squeezed to do it.
Although I criticize them in the book because they had growing pains, a lot of cancer centers are at the point where they could do this now and do this easily, and they have many more experts to do this than the FDA will ever have in their entire life. That, and the whole Compassionate Use Program, needs to be taken from the FDA and put back where it was in the 1970s.
Maurie Markman, MD: You’ve covered a lot of ground and you did, again, in the book very eloquently express your frustrations, including with your experience at cancer centers. One question is, and you sort of alluded to this, is the culture of the cancer centers changing, particularly those that are the matrix organizations that are not entirely focused on cancer and are more academically-oriented. Is that changing?
I guess a question is, “do we need to sort of rethink not the cost of the cancer centers, but the way they’re structured and organized, who is in charge, how you fund them and why you fund them?”
Vincent T. Devita Jr, MD: The answer is yes and yes. The long answer would take another hour. The answer is yes. I mean, I’m at Yale. I criticized Yale a lot. The deficit they have for having me at that institution is that I could see it firsthand, and I could describe what was wrong with it. We have come a long way and we’re really much better in terms of the emphasis on the application of the results of research.
When I went to Yale, they were concerned with doing research, but the application side was very neglected and it was very hard to get it going. Now, Roy Herbst is our chief of Medical Oncology. He is doing a wonderful job in application of results. So, yes, they are changing.
But, not all. I’ve just recently had an experience in a cancer center in this country, that I won’t mention where they had no essence of teams. All of our cancer centers have teams of people working. If you have lung cancer, you are seen by a team of people. At this center, there was nothing even resembling a team and a patient was just going from one doctor to another in sequence. I think that they’ve come a long way. I think they could handle the delegation of clinical trials to cancer centers.
Maurie Markman, MD: Now, I want to turn to research. I’m going to ask you—it’s unfair but I’m going to do it anyway—ask you to put on your crystal ball. We talked about immunotherapy. Again, it’s just having been in the immunology branch all those years ago and we thought we could cure cancer. Remember, we had a trial that was BCG and neuraminidase-treated tumor cells. I mean, my God, when you think about that now we say, “I can’t believe it.” But, where we are now is incredible. Obviously, we’ve learned a lot. Then, there’s this whole area of precision medicine and genomics and proteomics. Where do you think this is going to go? What is the future? Is it immunotherapy? Is it targeted therapy? Is it a combination? Based on your experience and what you see, what do you think?
Vincent T. Devita Jr, MD: In the next to the last chapter of the book—I call it “The Death of Cancer”—I go over the 8 hallmarks of cancer that Drs Weinberg and Hanahan wrote about in a landmark paper and point out that, when we’re successful, we’re attacking 2 or 3 of the hallmarks. In the future, we’re going to have to be thinking about attacking all of the hallmarks. Immunotherapy is just one. Failure of immunosurveillance is one of them. It was in 1996, I believe, when the discovery of the checkpoint inhibitors changed our whole thinking. We struggled for years trying to figure out why we couldn’t boost the immune system to eradicate cancer.
When Dr Steve Rosenberg did IL-2 with the infusions of lymphocytes, and you got marvelous responses in 10% or 15% of the patients but the rest of them didn’t get any, we couldn’t figure out what was going on. Jim Allison, PhD, solved the problem for us because he pointed out the existence of checkpoints.
Now, we have checkpoint inhibitors that are already on the market and it’s changed the face of immunotherapy. I don’t think immunotherapy by itself will be just the answer to cancer. I think it’ll be coupled with chemotherapy and other forms of treatment, if we have the freedom to put that together. As I say in the book on anti-hallmark therapy, “good luck in the current regulatory environment.” The FDA forces drug companies to test their drugs one at a time. What you need to do is test things in combination.
Maurie Markman, MD: Can we fix that? Yes.
Vincent T. Devita Jr, MD: If you delegated the phase I and II clinical trials to cancer centers, you could do it any way you wanted to. All we had to do was assure the safety of patients and have the effective oversight, and we all have our health, our human investigation committees. Yes, you could. It’s fixable. It’s fixable pretty quickly, and it’s fixable at less cost than the current cost. Here, we have an idea that actually would work and cost less money and would advance the cause of cancer treatment prevention, diagnosis by a great deal.
Maurie Markman, MD: Comment about the concept of cancer prevention. It’s very difficult to do and it’s very difficult to prove. Any comment about the future of cancer prevention, from your perspective?
Vincent T. Devita Jr, MD: Yeah. There’s no question. Everybody would rather not have cancer than have it. It’s just hard to prove that negative and prevention studies are very expensive. I remember when we first began to think about fat in the diet and breast cancer when I was at the National Cancer Institute. People were saying to spend money on prevention. We said, “okay, we’ll develop a clinical trial to look at low-fat diets compared to standard diets and see if we could reduce the incidence of breast cancer.”
I had the people work it up, and then I presented it to the board and said, “Okay, you want to do it? We need your approval. It’s going to cost $150 million.” They almost died; $150 million and the odds of it succeeding were probably between slim and none. They’re very expensive studies and you have leads that are not as solid as you’d like. We do know one thing: if you don’t smoke, your chances of dying of cancer are way, way less.
One of my beefs—and on the line of beef and pork—there is a lot of literature recently about bacon and the risk of colon cancer. I get emails from people asking, “what do you do?” It’s true. If you ate bacon every day, your risk of colon cancer would be up a little bit. But, if you’re facing a patient who is smoking and you tell them that they should stop eating bacon and eat less beef, and you don’t stop them from smoking, what will happen? If you put them on a scale, bacon’s down here and smoking is up through the ceiling, we know that if you stop people from smoking it works. Lung cancer mortality is dropping largely because of smoking cessation.
We could still do a lot. We could still drop mortality from cancer another 30% if we just completely stopped smoking. But otherwise, it’s a very difficult thing to do. We do have chemoprevention now with the drugs that seem to accelerate the decline and the risk of cancer. One of the unstudied areas is looking at chemoprevention in people who quit smoking. It takes 15 years for the risk of lung cancer to go down to near baseline, if you quit smoking, and maybe 10 years for head and neck cancer. But, still, it takes time.
If you gave these people chemopreventive agents, would you be able to accelerate the decline and the risk so that they would go down to baseline level in 5 years? We don’t really have studies like that, and I think we could do them. It would be important for two things. One, it would prevent cancer sooner. Second, we have great motivation for people to quit smoking. A lot of people tell you, “I’ve smoked so long, what difference does it make?” The answer is, it makes a difference even if you stop it. If you stop it and you take a chemopreventive agent then, maybe in 5 years, all your risk is gone.
Maurie Markman, MD: How does it feel to have been named one of the original Giants of Cancer Care several years ago?
Vincent T. Devita Jr, MD: It is a great accolade. It is nice to be recognized by your peers, and the company was pretty heady company. All of the people I’ve admired over the years were in that group and continue to be added to the group. It is a great honor, and I think people look forward to being considered a Giant of Cancer Care.
Maurie Markman, MD: Vincent, with your many years as a teacher, an organizer in medicine, as a researcher, what would you consider to be some of the major advances and breakthroughs, over these many years?
Vincent T. Devita Jr, MD: There are almost too many to mention if you look across the field. But, if you think of cancer treatment, there have been 3 paradigm shifts that I think have made a major impact. The first was the ability to cure advanced cancer with combination chemotherapy. That opened up the whole field of adjuvant treatment for breast cancer and colorectal cancer.
The second was when Brian Druker put targeted therapy on the map in chronic myelocytic leukemia with a drug that hit the Bcr-Abl mutation. That entered, in came targeted therapy, and we’re now using that approach in lung cancer, melanoma, and lots of cancers as we sequence the genome and find the targets.
The third has been the discovery of checkpoints in immunotherapy. Those are the three paradigm shifts that occurred in cancer treatment in my lifetime that are all having a significant impact on the ability to treat cancer.
Maurie Markman, MD: Just one final question. What are you doing these days? Obviously, you wrote your book and I know you’re still active in talking to audiences like this. How do you spend your time?
Vincent T. Devita Jr, MD: We put out this Principles and Practices of Oncology. We’re just starting the 11th edition. I don’t know why I’m doing this, but but it’s great fun because it keeps me up to date. The way we prepare the book with 3 editors and so on is a tedious but important process, and a learning process for me so I spend a lot of time doing that. You saw that the book took a lot of time. I see patients in consultation. I don’t follow them any more, so I’ll see them in consultation and then turn them over to a younger doctor that could take care of them. And, I teach. It’s part of the benefit of growing older, you have more time to sit back and look at the field and make judgments about it.
Maurie Markman, MD: Vince, I just can’t thank you enough. At a personal level, as a teacher of me, of generations of oncologists —medical oncologists, surgical oncologists, and radiation oncologists—and with what you’ve done for current patients and future patients, you are absolutely a Giant of Cancer Care. It’s been an honor for me to know, to work under you, and I thank you very much.
Vincent T. Devita Jr, MD: You’re very kind to say that, Maurie. It’s good to see you.