publication date: Nov. 6, 2015

DeVita: 50 Years of Stories

On Cancer Wars and Skirmishes 

 

Vince DeVita’s going-away portrait as NCI director. It hangs on the 13th floor at NCI.

(Credit: Mike Mitchell, cancer.gov.)


 

Vincent T. DeVita Jr. has seen the cancer field as a confident young doc eager to challenge the system, as a general in the War on Cancer, as an academic oncologist and, most recently, as a patient.

“I’ve been in a unique position. Partly, the War on Cancer happened because of what we were doing. I watched it grow, and then I ran it at the NCI. And then I came out of the NCI and I watched it from a private cancer center and a university cancer center,” said DeVita, co-author, with his daughter, Elizabeth DeVita-Raeburn, of The Death of Cancer: After Fifty Years on the Front Lines of Medicine, a Pioneering Oncologist Reveals Why the War on Cancer Is Winnable—and How We Can Get There, a just-published memoir.

“There are very few people who have been in that position. But I felt I owed it to the field to give a description of how I saw it, from the beginning to watching it from the outside—watching the field go through some very exciting times.”

DeVita, 80, served as director of the NCI from 1980 to 1988. Currently, he is the Amy and Joseph Perella Professor of Medicine and a professor of epidemiology and public health at the Yale School of Medicine.

He spoke with Paul Goldberg, editor and publisher of The Cancer Letter.

Paul Goldberg: Here at The Cancer Letter we don’t usually cover books, probably because so many of our readers write them, but this book is special. It’s a robust history of early triumphs at NCI and the beginning of the War on Cancer. I think everybody should read it. How long have you been working on it?

Vincent T. DeVita: I’ve been talking about it for at least 20 years. But the actual writing was relatively short, over about a two-year period. My daughter and I used to sit and talk about the stories, and which ones were good and which ones were not. We’ve been doing that on and off for a very long time.

But then we signed a contract with Farrar, Straus and Giroux, and we started to write. Then we slowed down for a while, but about two years ago we kicked into high gear and finished it. The actual writing itself did not take long.

The editing is a different story: I had a written something like 320,000 words; that would be an almost 900-page book that no one would read. So my daughter had the job of cutting it down to size, and smoothing it out. She did a really great job.

PG: Were you writing in real time at all, back in the 70s? Did you keep diaries, archives? Are you a pack rat?

VTD: Most of it I did from memory, but I can qualify that. Years ago, when I was director of the DCT [NCI Division of Cancer Treatment], my college contacted me and asked me to submit my papers. They said I was a distinguished graduate and asked if they could collect my papers. And I said to them, what’s important is the War on Cancer, and could I submit the papers for the War on Cancer? They said that would be fine.

So it turns out there were files—a few on the drug development program, that were to be discarded, but I resurrected them and sent them down to the College of William and Mary.

PG: So your records and archives are at William and Mary? 

VTD: Right. And I kept doing that. As [NCI] director [from 1980 to 1988], I kept moving correspondence down there. And I have a big collection of stuff here. So over the years, I put a lot into it, so I knew it. And all I had to do when we wrote the book was to pull it out and verify it.

So yes, when I typed, I didn’t type from a memo or from something like that, I typed it from memory, but I already had collected all this material over time.

PG: Some of these stories are so vivid. Like the story of Jay Freireich, mixing martinis, and Tom Frei walking drunkenly on his hands, and I’m quoting here, “his long legs in the air,” that’s just a hoot. And then there’s this other bit: the Society of Jabbering of Idiots, that’s really priceless.

VTD: The Society of Jabbering Idiots—it was a quote by George Canellos [a colleague at NCI]—was a room where everyone tried to talk at once. But it was a very exciting meeting.

I tell people here, I don’t think I’ve ever attended a more exciting meeting than that—or a meeting that turned out to be more productive–because we were able to take things that we decided on in that room and put out a protocol the next day. You can’t do that sort of thing anymore.

And then [NCI childhood leukemia researchers] Frei and Freireich, and I wrote a note to Jay—because he comes out as a hero in the book—telling him that he might be uncomfortable with these stories, but what it shows is that they were so intense, you know, they worked very hard, and they played very hard.

It was a revelation to watch them. They really were very intense individuals. I’m very fond of Jay Freireich. I owe him a lot. He was a good role model for me.

  

George Canellos, DeVita, and Robert Young, left-to-right, circa 1971. By this time, Canellos and DeVita were working on combination chemotherapy for breast cancer. Young was in charge of chemotherapy for early-stage Hodgkin’s disease and the ovarian cancer program. (Credit: Joel Carl Freid.)


 

PG: This is an epistemological question: Did you realize in real time that you were making medical history?

VTD: There had been a paper that came out—I think it was in The Lancet, or British Medical Journal—by two radiotherapists who used the word “cure” in the title, referring to the cure of Hodgkin’s disease.

And there was a big stir, because people were afraid to use the word “cure.” And we were looking at the leukemia work that was going on, and so we designed the MOMP program and the MOPP program to be cures. And that was unusual, and at the time we knew that if we succeeded it would be unusual.

It was a bit cheeky, I think, for two young guys [DeVita and John Moxley] to do that. We weren’t sure we would succeed, but we certainly wanted to try. And the thing about the NIH in those days was that you could do that sort of thing. You had the resources to do it. You could bring patients in from all over the country, and keep them there, and be self-limited by what was going on between your ears.

So we had a sense of that. I keep in touch with Jack Moxley, and he feels the same way. We were two cocky guys who thought we were pretty smart, so I look back on those days very fondly with Jack.

PG: It’s interesting because it’s the only book that—and I think I’ve pretty much read everything there is on this subject—and the only material that’s close in terms of its detail is the interview that Jay Freireich gave John Laszlo in a book about childhood leukemia, and Laszlo basically kept the tape recorder running. And it’s just basically a transcript. It’s been mined and mined and mined by many people, including me.

VTD: We interviewed Jay when Elizabeth and I went to ASCO [annual meeting] and we interviewed Jay for something like four hours. So we have very similar transcripts.

But also I remember Jay as a very vivid character, and I remember him very well. I trained 93 medical oncologists when we were at the NCI, and sometimes when I meet with them, they say to me, “Dr. DeVita,” because they still try to call me Dr. DeVita, “Do you remember when we were standing by the bed for Mrs. Jones, and you told me the following, and I’ve never forgotten it.” And I look at him and I say, “Sure,” but I don’t remember a thing about it. Because when you’re training people you say things, and it makes an impact on them and sometimes the impact just stays with you.

Jay had those kinds of impacts on me.

I think there’s one thing in the book that Jay doesn’t agree with in terms of our meeting, but I remember it very vividly. I think those are the kind of things that maybe Jay wouldn’t give in an interview, because there was no impact on him, the impact was on somebody else.

But he had a laugh about me standing there with me pointing at the label of Polymyxin bottles saying don’t give intrathecally, and having Jay point at me and say “Give it.” He probably wouldn’t remember that, but the fact of the matter is that he did. And I just remember it so well, because it was such a vivid departure from what you normally did. He was at once a very commanding and very terrifying figure.

PG: Well here’s kind of a—speaking of commanding and terrifying figures—Mary Lasker, here’s a wealthy socialite who uses the methods of public relations to declare the War on Cancer, and she promises the cure by the bicentennial, she and her friends.

Do you think she actually knew this couldn’t be done?

VTD: I don’t know. She was a very smart woman.

I never said to her, “Mary, we’ll do our best, but you know it can’t be done.” That would have been foolhardy, because Mary didn’t like people who were negative. So we didn’t approach it that way. My feeling is she did know. But she never said she knew. She always felt that the end justified the means.

That’s how she operated. We all kind of operated on the assumption and didn’t have to explain it, because everyone knew it couldn’t possibly be done. We couldn’t get money going to the labs until 1974, two years before the bicentennial. I mean it was an impossible feat. But some people in the press and some people in Congress did really believe it. And they never let us forget it.

PG: This expectation, which some people in the media, as you said, took literally—and how else are you going to take it? This caused serious problems for you at NCI. In retrospect, was it worth it to build up expectations like this?

VTD: I think the War on Cancer was worth it. Whether it would have happened if she said this would happen over 10 or 20 years, I don’t know. I think the War on Cancer was a grand experiment and it worked.

The NIH was very much against it. But so many things at the NIH now happened because of the War on Cancer. It was a transformational program for the whole institution.

So I think the program was worth it. I think a little bit more honesty would have been better; it would have taken a little bit of heat off us, but I can’t answer that question with any surety. 

 

The gang of five at the Medicine Branch in 1973. From left to right: George Canellos, Bruce Chabner, Philip Schein, DeVita, and Robert Young.


 

PG: It’s an opinion, of course. I guess what’s also amazing is this bit about you being called in to give a science lecture to Sen. [Warren] Magnuson’s chauffeur, so that he would bring it up with Mrs. Magnuson, who would then bring it up with the senator. [Magnuson, a Minnesota Democrat, was a powerful appropriator.] So the whole message was surrounding him.

VTD: That was only one of several. I used to be invited on a regular basis to [Washington hostess] Deeda Blair’s house for lunch, and that was Mary Lasker’s tactic. Mary used to come to Washington and stay at Deeda’s house.

That was a favorite tactic of hers. She never did leave any stone unturned. Because all through the lunch, I didn’t know who he was, and so forth. It was a big black car that pulled up in front of the house, so when Mary told me that that was Maggy’s driver, I was quite shocked, and she saw it. She looked at me and put her hand up, and said, “Wait a minute, he drives Maggy’s wife around all day and she puts her head down on the pillow at night next to Maggy.” I would shake my head at this woman. She was so thorough.

PG: It’s amazing that we’re still in dialogue with Mary Lasker, and in some ways this book is. You end with an analysis of your thoughts of Mary Lasker. But I guess there is something about her thinking that is still there. What do you think of the more recent plan to end suffering and death due to cancer by 2015, which is almost over? Should future deadlines be less specific, or should this be a game that any of us should play?

VTD: Well, you know we set goals for the year 2000. We published a monograph about the way this could happen, and then tried to remind people that they were goals, not estimates.

Goals we have to sit down and say—and let’s use mammography as an example—when we sat down in 1984, 14 percent of women who were supposed to be screened by mammography were being screened. We thought we had to get up to 70 percent before 1990 to be able to decrease mortality in women with breast cancer by a significant degree by the year 2000. So we would have to set up programs to support the use of mammography screening, and also get on the bully pulpit and do it.

 

DeVita with former President Richard Nixon.
“I asked him what he thought were the greatest
achievements of his presidency,” DeVita said.
“He said going to China and signing the National Cancer Act.”

So it wasn’t a matter of saying, okay, we’re going to drop mortality because we’re going to screen more people—these were goals, not estimates. So I think the mistake is when you make a pronouncement or a prediction of what will happen, and don’t back it up with information about how you get there.

We said in that monograph that [former director of the NCI Division of Cancer Prevention and Control] Peter Greenwald and I published, if you did everything that you could do in the country simultaneously, which we knew was impossible, you could get a 50 percent reduction in mortality. We thought, realistically, if we got 25 percent we’d be very pleased. And I think the actual figure was something like 16 percent.

You have to keep in mind that, at the time we did that, my advisors at the NCI were telling me that the incidence and the mortality rate was a straight line going straight up to the year 2000. They said there was not going to be any decrease; there was no way we could decrease it. So getting any decrease in mortality by the year 2000 was an achievement.

But it was a goal, it wasn’t an estimate.

PG: The year 2015 was also a goal and an estimate.

VTD: Yeah, but there was nothing to it.

There was no “To end death and suffering, we have to do the following five things…”

And we have to identify what you mean by death and suffering. Death is clear: mortality statistics—but suffering?

It was so vague that—and you’re referring to [former NCI Director Andrew] von Eschenbach’s goal—it was so unclear what he actually meant, that it was clear to everybody that nothing of value that would ever come of it.

And, to be honest, I like Andy, but it sort of discredited us setting goals.

I think the American Cancer Society goals were very realistic. They looked at what the trends were and what programs they had in place and what they could manipulate—and most of the disease-specific goals were reached, or are very close to being reached.

I think they’re helpful if you do that. And one of the reasons I did it, because the government is in the habit of spending money without any benchmark as to how well you’re doing. So I think you need to set benchmarks.

So I like goals, but you have to be very careful. We took a lot of criticism when we set up goals for the year 2000 in 1984.

PG: I hope you don’t mind a small tangent here. This is a tangent because of Mary Lasker—what are your thoughts on the current state of the American Cancer Society, and how does it become as relevant as it was in her days?

VTD: I think the new CEO is a terrific guy. I like Gary [Reedy] a lot. I think he will do a terrific job. But they had started to lose their way, I think, over a number of years. I think they need to be very careful about retaining their supporters. Most of their support comes from people who give small donations.

I was there when we did the transformation of the ACS and we centralized much of it. And the main concern was that they would lose contact with supporters. I haven’t kept in touch with how well they’re doing in terms of income over the last couple of years, so I don’t know whether it’s continued to go down—it went from a billion dollars down to about $800 million, which is a big drop.

And my beef with them always—and they had, supposedly, before I left, set up programs to correct this—my beef with them is that I didn’t think they put enough money into support of basic research and the grant program.

DeVita with Mary Lasker.

 

PG: I remember when Mary bought it from the surgeons, she sent them huge amounts of money—what was it, 75 percent? It’s in your book.

VTD: No, no, no, she actually said something like 25 percent. And for a long time, the American Cancer Society contributed 20 to 22 percent of their money to extramural grants; grants that go to scientists on the outside. Now they’re down to 10 percent, and I think that’s a mistake.

And we set in motion a plan to double that over 10 years as I left the board. I hope they’re staying with it.

When you listen to the advertising of the American Cancer Society, they talk about how many Nobel laureates they support and so forth. And then you look at how 10 percent of their money goes to support extramural grants—there’s a very severe mismatch there.

If I know Gary, he will change that, but it’s going to take some time.

PG: Let’s go back to your book, but thanks for the tangent.

In a version that didn’t make it into law, the National Cancer Act would have taken approval authority for cancer drugs out of the FDA and put it in the institute. Do you think this schema would have worked better than what we got?

VTD: Yes… Do you want an explanation?

PG: Please.

VTD: I have made the case many times to the FDA, pleaded with them, that cancer patients were different.

They’re different from patients with hypertension; they’re different than patients who have high cholesterol, anemia, or diabetes. They’re different than patients with arthritis.

These people have chronic diseases that are not curable—when you have arthritis you have it for your entire life, but you can manage it. And the people live and in many cases do live a normal life.

Cancer is the most curable chronic disease and it’s the most fatal chronic disease. You need to deal with patients who are facing death in six months to a year differently than you deal with developing drugs for patients who have arthritis.

The FDA has always said, “No, if we do it for you, we have to do it for everybody else”—and that’s nonsense, that assumes that you have no judgment at all, and that you just follow the line. So we never did it.

I think if we moved the drug development approvals to the NCI, where we have expertise, it would have been a major change into how we develop drugs. And as I point out in the book, I think one of the main problems getting in the way of progress right now is the fact that everything is centralized at the FDA and the NCI.

Cancer centers were developed to be small replicas of the NCI, to be independent scientific bases that could apply what they learned in practice. And they need to have the flexibility to move very quickly, especially in the early-phase clinical trials.

So I think now, today, the NCI and the FDA should delegate all authority for phase I and II trials to the cancer centers, and let them make all their adjustments based on their own expertise. The NCI and the FDA retain the right to come in and audit at any time, but all the cancer centers have really spent years getting their trial programs up to snuff—and when they’re reviewed, it’s a big part of the review to see if they have their clinical trials program in shape.

So they’re there now, and they could do that. I think it was a problem then, and I think it’s a problem now.

PG: In the book you refer to the Frances Kelsey syndrome, describing the FDA stance as exceedingly risk-averse.

I cover FDA closely, and I see the agency approving drugs at a pretty rapid rate these days. I can barely keep track. I think their philosophy is influenced by evolving science in cancer, and it seems to be really moving towards activism. Do you see it otherwise?

VTD: Yes I do. Do you want an explanation for that, too?

PG: Please.

VTD: I am giving a talk to the fellows here, and I do it every year, and I’ll be going over the book.

One of the things I’m going to say to them is that, you think you’re the doctors of the patients, but you’re not. The FDA is the doctor. You don’t do anything that the FDA doesn’t approve.

And the thing that struck me recently was the approval of the use of two checkpoint inhibitors, the anti-PD-1 and the anti-CTLA4 together. The FDA approved the combination, and nobody noticed.

Now you have the FDA approving the use of approved drugs in combination—where these drugs are both approved for the disease, and now you have to go to them to get approval for a protocol and approval for the use of that.

If that had been in place when we were developing MOPP, if we were persistent it would have taken us a minimum of 10 to 15 years to develop the MOPP program. You don’t realize it, but it’s a very subtle thing, but the FDA has sort of paralyzed clinical investigation because no one can do anything without going through these myriad approval processes. I think it’s ludicrous.

There’s another one I can’t recall, but I just saw it, another approval of another drug combination. I can see the FDA approving drugs that are packaged in one pill or two drugs given together as a formula, but to take drugs that are approved individually for the diseases, and to require investigators to get approval for the testing and the approval to use them in practice, I think is a very serious backward step.

Basically you’re having them approve the combination of radiation therapy or chemotherapy or a targeted therapy. In fact, I’ve heard rumbles about having to do it. These guys are so far away from the patient that they have no business doing that.

PG: But off-label use is fine though.

VTD: Off-label use—okay, then tell me why the combination of ipilimumab and nivolumab was approved by the Food and Drug Administration?

PG: I’m just going to take a stab at it, and I’m probably going to guess it wrong, but I think the rationale would be so it would get on the label, because the sponsors wanted it on the label so they could get paid.

VTD: Well I think you did quite well. It’s a vicious cycle.

If the drugs are approved, and the FDA doesn’t approve combinations, they’ll get paid; if it works the insurance companies will pay for them. 

DeVita talking over lab results with a
researcher at Yale.
On the viewbox are her
electrophoretic gels, which separate molecules
by size and electric charge.

But do you realize how much longer it takes to get these things—it also inhibits the process. I can’t do something if I have to send it to the FDA, I have to send it to the IRB, to my cancer center approval committee, and then I have to send it to the NCI.

So you go through these various approval processes and you’re thinking about the protocols—and I have to send it to the IRB, but they don’t like these kind of protocols, so I’m not going to put this together. It slows down the process tremendously.

The sad thing about it is that we’ve just come to accept it. It’s not necessary for patient safety. It’s just totally unnecessary.

PG: So you’re exactly where Jay Freireich is on this issue?

VTD: I haven’t discussed it with Jay Freireich, to be honest with you. But I’m not surprised if we are. I’m sort of a clone of Jay Freireich.

PG: You’ve criticized FDA for excessive reliance on the overall survival metric, which requires randomized trials, but this reliance has made it possible to approve drugs based on metrics of slowing disease progression.

Is it wrong to rely on randomization in the regulatory setting? And I guess before I shut up, you seem to admire Bernie Fisher for his reliance on randomization in clinical research, but you seem to be less admiring of Chuck Moertel pushing FDA towards reliance on survival, so is there a difference?

I think both of these guys are giants in exactly the same way, and I could be wrong. Am I?

VTD: They’re both great friends of mine. The late Chuck Moertel—I used to tell people that when things got hot, and I looked around to see who was still standing to give me a hand, and Chuck Moertel [director of the Mayo Clinic Cancer Center and member of the FDA Oncologic Drugs Advisory Committee] was always there.

And he’s a great friend of mine, but he was totally wrong about what he did. And it wasn’t randomized trials, and it wasn’t even just the survival, he approached it from a very negative point of view. I guess it was Henry Kaplan [radiologist who pioneered radiation therapy] who used to say to me, “If it’s not worth doing, it’s not worth doing well.”

Chuck Moertel would design randomized trials that were ridiculous in terms of how he used 5-fluorouracil. He would use 5-fluorouracil five days every six weeks, because that’s the way the referral system at the Mayo Clinic worked. And it was magic.

I actually wrote a piece, he and I wrote—he was a thespian, he was a great actor, and he would deliver these speeches and wow the audience, and I used to write these counter-speeches—and I wrote one about the ability to believe in magic. So what good was the randomized controlled trial when the premise behind the trial was completely insane? And nor would any human investigations committee know that.

Because most of them just don’t have the kind of staffing that would say, “Wait a minute, it’s a randomized trial, but the trial itself is crazy. That’s where guys like Chuck Moertel were saying let me look at survival as an endpoint. I admire Bernie Fisher [pioneering breast cancer researcher and founder of the National Surgical Adjuvant Breast and Bowel Program] a great deal—and look, I believe randomized controlled trials are a gold standard, and absolutely necessary under certain circumstances, but not under every circumstance.

PG: But this case, right now, the reason you see this huge number of approvals is because of the randomized trials, which are allowing you to see whether drugs are actually slowing down disease progression.

VTD: No I don’t think so. I think it’s because they’re targeted therapies. And they’re easier for the FDA to swallow, because they have a specific target to shoot at. As a matter of fact, if they weren’t targeted therapies, most of these drugs wouldn’t get approved by the FDA, because by themselves they’re often very poor. They need to be used in combination with some other drug. So I think that it’s more of an illusion.

Mind you, what I said before: phase I and phase II trials should be delegated to the cancer centers. Most of them are not randomized; some of them are. The phase III trials, which are randomized, are different. They’re bigger studies and they’re the studies that go for NDA approval, and I think these should still be under the purview of the FDA and the NCI. Yes, I’m very happy that the FDA is approving drugs more rapidly, but we’re in a situation now where we have proof of principle.

In general, the combinations of drugs are equal or are better than using them alone. We really want to encourage that kind of research, and that’s not being encouraged by the Food and Drug Administration. They want you to get individual drug data for approval. That was the point that I made, among a number of other things, in that FDA chapter.

PG: There are these wonderful anecdotes in the book. Which one would you say, if you were to look at all of it, what would be the most spectacular mistake you’ve made as a physician or as a policymaker?

VTD: I used to keep track, honestly, of major decisions, and I calculated that about 80 percent of the time, I made a really good decision. And 20 percent of the time I didn’t. I’ve made so many decisions I can’t even tell you which one was which at the moment. I don’t really recall any of the spectacular mistakes, do you?

PG: No. I didn’t see any in the book. So 80-20 is pretty good!

VTD: I thought it was pretty good. I would say 20 percent of the time I wish I could do it over again. They weren’t always disastrous, but they weren’t always the most productive things. I used to keep track of the total and I don’t have a list of them anymore, but that’s pretty good. Fifty-fifty you can just do with a coin.

PG: Fifty-fifty is pretty good. I’m striving for that.

You’ve seen the development of this field, both as a heroic doc and as a policymaker. Now that you are seeing it as a prostate cancer survivor, how is it different?

VTD: I recapped a lot of the problems I’ve had, if I hadn’t been who I am, I’d be dead by now. It shows me we have a long way to go to navigate patients through a field like cancer treatment, which is evolving so rapidly. The thing about the field now is that there are so many things happening.

When they happen they don’t happen universally at the same time across the country. When you get a new anti-PD1 inhibitor, it’s imported from a center or maybe a group of five centers; it’s not universally available across the country.

I just found out first hand, in my own case—my sister developed non-small cell lung cancer. She was a candidate for the PD1 inhibitors, and no matter what I did, I could not get her doctors to get access to it, even though she was an eligible patient study-wise: she had failed her first round of combination doublets for non-small cell lung cancer.

She died in May without access to drugs that were approved a few months later. And part of the problem was the doctors did not want to buck the system and get in trouble with their human investigations committee or get in trouble with the FDA to be able to do it. It was a big disappointment on my part.

PG: This book is really entirely about you fighting the establishment and the conservatives in the medical field.

VTD: Well, it’s a description of those things. I have played some role. I didn’t fight everything.

I’ve been in a unique position. Partly the War on Cancer happened because of what we were doing. I watched it grow, and then I ran it at the NCI. And then I came out of the NCI and I watched it from a private cancer center and a university cancer center.

There are very few people who have been in that position. But I felt I owed it to the field to give a description of how I saw it, from the beginning to watching it from the outside—watching the field go through some very exciting times.

PG: And that was why I couldn’t put the book down. Thank you.

Copyright (c) 2018 The Cancer Letter Inc.