Killing Cancer
Editor's Note: For more information on the Duke University polio trial or other brain cancer trials, click here or call 919-684-5301
The following script is from "Killing Cancer" which aired on March 29, 2015. Scott Pelley is the correspondent. Michael Radutzky and Denise Schrier Cetta, producers.
The long war on cancer has left us well short of victory. Radiation flashed on in the 19th century, chemotherapy began to drip in the 20th but, for so many, 100 years of research adds up to just a few more months of life. Well tonight, you're about see a discovery for the 21st century that may be a big leap forward --awakening the power of the body's immune system.
For 10 months, we've been inside an experimental therapy at Duke University. Some of the patients there use words that doctors don't use, like "miracle" and "cure." And that's remarkable, because these patients were handed a death sentence, a relentless brain cancer called glioblastoma. To beat it, researchers are doing something that many thought was crazy, they are infecting the tumors with polio -- the virus that has crippled and killed for centuries.
In just a moment, polio will be dripped into the brain of 58-year-old Nancy Justice. Her glioblastoma tumor was discovered in 2012. Surgery, chemotherapy and radiation bought her two and a half years. But the tumor came roaring back. Now, the virus in this syringe, which mankind has fought to eradicate from the earth, is the last chance she has in the world.
[Nurse: You might feel a little tug.]
In October this past year, half a teaspoon of polio flowed into her tumor.
Nurse: OK. Ready to go?
Nancy Justice: I'm ready, bring it on.
Nurse: We're starting, 9:21.
"I'm taking it one day at a time. It sounds very lofty to say medical explorer. But, you know, throughout all of this, if this gives other people hope I'm all for it."
Dr. Annick Desjardins: If you feel anything you let us know.
Nancy Justice: I will definitely.
Dr. Annick Desjardins: Perfect.
Scott Pelley: Well, lemme ask do you feel anything?
Nancy Justice: No. So far so good. Don't feel a thing.
Her husband, Greg, constantly inflates a buoyant optimism to save him from the weight of the unknown. Glioblastoma was diagnosed in the 21st year of the Georgia couple's marriage -- just as they could make out the finish line for Zach and Luke at college. Her tumor can double in size every two weeks. And when glioblastoma returns -- time is short -- doctors gave her seven months. But good ones? Maybe just three or four.
Scott Pelley: The tumor was aggressive--
Nancy Justice: Yes.
Scott Pelley: So you wanted an aggressive treatment--
Nancy Justice: Yes. Yes.
Scott Pelley: You're-- a medical explorer. Does it feel that way to you?
Nancy Justice: I'm taking it one day at a time. It sounds very lofty to say medical explorer. But, you know, throughout all of this, if this gives other people hope I'm all for it.
Scott Pelley: Greg, you mentioned that Nancy was there for every important event in the boys' lives.
Greg Justice: Right.
Scott Pelley: But there a lot of important events to come.
Greg Justice: Exactly.
Scott Pelley: What do you hope to see?
Nancy Justice: So I am gonna see those boys walk across the stage at their college graduation. I am gonna see 'em get married. And I am gonna see the grandkids, preferably in that order. And I know it's, like, such a mom bucket list. But I'll love every minute of it.
It was the day before, that we saw Nancy preceded by her shield--the smile that she rarely lets slip.
Nancy Justice: I'm ready.
Nancy was wheeling into an intricate surgery to insert a path for the virus. That white mass is the tumor, back of her skull, near the top. Duke's Chief of Neurosurgery Dr. John Sampson, used 3D MRIs to plot his course. He tacked between the lime-green strands that connect to every vital function in her body. And he brought the catheter to the center of the lethal mass.
Dr. John Sampson: It's just like a sniper's bullet. If it doesn't go to the right place, it's not gonna hit the target. And it's not only important to get it to the right place, but also to make sure that it doesn't go to the wrong places, doesn't cause any harm to the patient.
Scott Pelley: It doesn't travel throughout the brain?
Dr. John Sampson: It won't travel too far throughout the brain, because it's a relatively big molecule and the brain's a tight space, so it's limited in how far it can travel.
At least, that's what they expected, as Nancy became the 17th patient in the experiment. The polio infusion was slow, that half a teaspoon took six and a half hours. But that's it, one dose and she's done. No more surgery, chemo, radiation, nothing--if this works.
Dr. Annick Desjardins: You're doing fantastic.
Nancy Justice: Alright.
Dr. Annick Desjardins: Now, show me your smile.
On Nancy's way home that same day, oncologist Dr. Annick Desjardins, showed her how it went.
Dr. Annick Desjardins: So we can exactly see where the polio virus went. So that's the MRI you and I looked at on Monday. Then you see here the brighter area there? Can you see that?
Nancy Justice: Yes.
Dr. Annick Desjardins: That's the polio virus.
Nancy Justice: Wow.
Dr. Annick Desjardins: Exactly where we needed it.
Nancy Justice: Oh. Cool. Okay.
Dr. Annick Desjardins: Right where it should be
In a few months, they'll take another MRI to see which is stronger, glioblastoma or polio.
Dr. Henry Friedman: The number of calls are increasing...
This is Duke's polio team. As usual in such studies, several of them have a financial stake so they'll benefit too if it becomes commercial. Can you pick out the deputy director of the brain tumor center? Well, when you're one of the world's leading cancer doctors, turns out you can wear what you like. And after 34 years, folks at Duke are used to how Dr. Henry Friedman's brain views fashion.
Dr. Henry Friedman: It's really good to see that things are going well.
It was Friedman who encouraged Nancy Justice to gamble on the polio experiment.
Scott Pelley: I wonder of all the trials and all of the theories and all of the treatments that you have hoped for all of these years, how does this stack up?
Dr. Henry Friedman: This, to me, is the most promising therapy I've seen in my career, period.
Scott Pelley: A turning point in cancer care?
Dr. Henry Friedman: I hope so. I think it may well be.
Why would he say that during an early clinical trial with barely enough patients to fill an elevator? Because of the decades of work that have led to this moment. The virus is the creation of, the obsession of, Dr. Matthias Gromeier, a molecular biologist who's been laboring over this therapy 25 years, the last 15 at duke.
Scott Pelley: When you went to your colleagues and said, "I've got it. We'll use the polio virus to kill cancer." What did they say?
Dr. Matthias Gromeier: Well, I got a range of responses from, from crazy to you're lying, to all kinds of things. Most people just thought it was too dangerous.
Dr. Henry Friedman: Oh, I thought he was nuts. I mean I really thought he was using a weapon that produces paralysis.
Other researchers are experimenting with cancer treatments using viruses including HIV, small pox and measles. But polio was Dr. Gromeier's choice because, as luck would have it, it seeks out and attaches to a receptor that is found on the surface of the cells that make up nearly every kind of solid tumor. It's almost as if polio had evolved for the purpose.
Gromeier re-engineered the polio virus by removing a key genetic sequence. The virus can't survive this way so he repaired the damage with a harmless bit of cold virus. This new modified virus can't cause paralysis or death because it can't reproduce in normal cells. But in cancer cells it does and in the process of replicating, it releases toxins that poison the cell. Duke went to the FDA for approval of this new Frankenstein virus.
Scott Pelley: They were afraid you might create a monster?
Dr. Henry Friedman: They were afraid we might create something which could infect the general community. I mean, look at me, I'm a scientist. I'm a physician. And I said, "this is nuts." I think that their reaction was appropriate.
To satisfy the FDA, they did seven years of safety studies. Tests on 39 monkeys proved they didn't get polio. And in 2011, the FDA approved a trial in humans. Someone had to go first.
It's a hell of a thing to be told that you have months to live when you're 20 years old. In 2011, Stephanie Lipscomb was a nursing student with headaches. A doctor came in to say that she had this glioblastoma tumor the size of a tennis ball.
Stephanie Lipscomb: I looked at the nurse that was sitting there holding my hand and I said, "I don't understand. Like, what did he just say?" It was kind of hard for me to process.
Scott Pelley: You had 98 percent of the tumor removed.
Stephanie Lipscomb: Exactly.
Scott Pelley: As much radiation as you can have in a lifetime. And chemotherapy.
Stephanie Lipscomb: Exactly.
Scott Pelley: And then in 2012, what did the doctors tell you?
Stephanie Lipscomb: Your cancer's back.
With recurrent glioblastoma, there were no options except the one that had never been tried before.
Scott Pelley: Did they tell you that it had never been tried in a human being before?
Stephanie Lipscomb: They did. But at the same time, I had nothing to lose, honestly.
Scott Pelley: I wonder what your mother said?
Stephanie Lipscomb: She looked at Dr. Desjardins and she said you want to do what with my daughter? You want to do what? And I'm like, "lets do it, come on, lets go."
Scott Pelley: I have the sense that this scared you a lot more than you've let on.
Stephanie Lipscomb: It did. I knew how scared my family was. And I didn't want it them to see me scared.
Scott Pelley: But of course, you were.
Stephanie Lipscomb: Un-huh.
Dr. Henry Friedman: In point of fact, we didn't know what the polio was gonna do. We thought the polio virus might help her. We had no idea what it would do in the long haul. It was a crap shoot. It's roll the dice and hope that you're gonna get an answer that is coming up sevens and not coming up snake eyes.
But in the months that followed it looked like a bad bet.
Dr. Annick Desjardins: So we treated her in May. Then in July the tumor looked bigger, looked really inflamed. I got really concerned, got really worried.
Scott Pelley: You thought this wasn't working.
Dr. Annick Desjardins: I thought it wasn't working.
Dr. Desjardins wanted to go back to traditional treatment - maybe another surgery -- but Stephanie decided, against her advice, to wait. By October, five months after her infusion, an MRI showed that the tumor hadn't been growing at all. It turned out it only looked worse because it was inflamed. Stephanie's immune system had awakened to the cancer and gone to war.
Scott Pelley: Why didn't the immune system react to the cancer to begin with?
Dr. Matthias Gromeier: So cancers, all human cancers, they develop a shield or shroud of protective measures that make them invisible to the immune system. And this is precisely what we try to reverse with our virus. So by infecting the tumor, we are actually removing this protective shield. And telling the-- enabling the immune system to come in and attack.
Scott Pelley: So essentially what's happening here inside the tumor is you have a polio infection.
Dr. Matthias Gromeier: Yes.
Scott Pelley: And that sets off an alarm
Dr. Matthias Gromeier: Yes.
Scott Pelley: For the immune system.
Dr. Matthias Gromeier: Yes
Scott Pelley: The immune system says, "There's a polio infection. We better go kill it."
Dr. Matthias Gromeier: Exactly.
Scott Pelley: And it turns out it's the tumor.
Dr. Matthias Gromeier: Yes.
It appears the polio starts the killing but it's the immune system that does most of the damage. Stephanie's tumor shrank for 21 months until it was gone. This is an MRI from this past August. Three years after the infusion, something unimaginable has happened for a patient with recurrent glioblastoma.
Scott Pelley: And there's no cancer in this picture at all--
Dr. Annick Desjardins: And we don't see any cancer, active cancer cells in this tumor at all.
She is cancer free. The only thing that remains is this hole, which is an artifact of an early surgery.
Scott Pelley: Under traditional standard-of-care treatment Stephanie should not be standing here next to us today?
Dr. Annick Desjardins: Absolutely not.
Scott Pelley: Stephanie, when they showed this to you what did you think?
Stephanie Lipscomb: I wanted to cry with excitement this time.
Scott Pelley: How surprised are you by that?
Dr. Henry Friedman: I'm surprised because you never expect on a Phase 1 study in particular, which is what she is on, to have these kinds of results.
Scott Pelley: You're not expecting to cure people in a Phase 1 trial.
Dr. Henry Friedman: You're not even necessarily expecting to help them. You hope so. But that's not the design of a Phase 1 study. It's designed to get the right dose. When you get anything on top of that its cake.
Scott Pelley: Quite a cake.
Dr. Henry Friedman: Quite a cake. Quite a cake. Biggest cake we've seen in a long, long time.
Scott Pelley: Tell me what you see there.
Dr. Fritz Andersen showed us the results in another patient -- himself. He's a retired cardiologist and at age 70, he became the second person in the polio trial.
Dr. Fritz Andersen: This is a fairly sizeable temporal tumor, which means...
Scott Pelley: That we see right here.
On the left is his tumor before treatment, on the right a hairline scar where it used to be. Like Stephanie, that was nearly three years ago.
Dr. Fritz Andersen: So when they said that this thing is just a small scar, and we think it's possibly cured. I nearly fell off my chair. I said, "that's, that's, that's impossible." They said, "well, we don't know, but so far it looks fantastic."
Scott Pelley: Do you consider yourself cured? Or do you call it remission?
Dr. Fritz Andersen: I feel it is a cure, and I live my life that way.
Fritz and Stephanie met for the first time here at 60 Minutes when we interviewed them last fall.
Dr. Fritz Andersen: We should do a head bump. There you go. There you go.
Stephanie Lipscomb: Was yours on the right side?
Dr. Fritz Andersen: No, on the left. Which one's yours?
Stephanie Lipscomb: My right.
Dr. Fritz Andersen: Well let do it, right to left. There we go.
With the early success the team raised the dose in the next few patients in hope of an even better result. But that's when the polio trial encountered its first tragedies. When we come back we'll look at how the virus is working in Nancy Justice, who we met in the beginning, and at what they've discovered after trying polio against lung cancer, breast cancer and many others.
Part two
For nearly a year we've been following the clinical trial at Duke University where the polio virus is being used to kill a vicious brain cancer called glioblastoma. The goal of the experiment was to discover the right dose of the virus. The first two patients saw their tumors melt away. So, with that remarkable result at small doses, the researchers increased the potency of the virus in the next patients. That's how they made a tragic, but vital discovery about the power of immunotherapy in killing cancer.
Dr. Annick Desjardins: Maybe you just close an eye...
It's been three years since Stephanie Lipscomb became the first patient to see her recurrent glioblastoma wiped out by polio.
Dr. Annick Desjardins: Problem with memory?
Stephanie Lipscomb: No.
Dr. Annick Desjardins: Vision?
Stephanie Lipscomb: No.
She gets a check up at Duke every four months.
Stephanie Lipscomb: Hey!
Donna Clegg: How are you?
Stephanie Lipscomb: Good.
And she's become a celebrity to the new patients starting the polio trial. Sixty-year-old Donna Clegg, a social worker from Idaho, will be patient number 14.
Donna Clegg: We're gonna do it!
Stephanie Lipscomb: Yes, high five.
Donna Clegg: Thank you.
This was Donna Clegg before cancer. And this is how we found her last June. Puffy from the steroids they used to limit the swelling in her brain. Like others in the trial, she'd had surgery, chemo, and radiation but the glioblastoma came back and the polio virus was her last chance.
Donna Clegg: I wanna be able to live. So that's kinda how I feel, that this is gonna be my opportunity to have a full life.
Donna's polio infusion was three times more potent than the one that worked for Stephanie. And that's the whole idea behind this Phase 1 trial--to increase the dose in succeeding patients, step by step, in search of the best result.
Dr. Henry Friedman is deputy director of Duke's Brain Tumor Center.
Dr. Henry Friedman: We believe in the philosophy we've learned in chemotherapy that more is better. So if we were getting a good response at dose level one or dose level two, then go to dose level three, four, five.
In Donna Clegg, doctors saw the expected inflammation as her immune system attacked the tumor. But the higher dose caused an immune response that was much too powerful. The inflammation put so much pressure on her brain she became partially paralyzed. Back home in Idaho she decided it was all too much and dropped out of the polio trial.
Donna Clegg: I thought this was the miracle.
Her husband recorded this in a nursing home.
Donna Clegg: When you're told you either take this chance or die, what would you do?
Wayne: If you had to do it over again, what would you do?
Donna Clegg: I may not have done it.
Donna Clegg died three weeks ago. Because she left the trial, doctors at Duke can only theorize that it was a combination of the advanced state of her disease and the ferocious immune response that ended her life.
Scott Pelley: Donna Clegg suffered quite a lot. And I wonder how that weighs on your mind?
Dr. Henry Friedman: Every patient who has an outcome that is not positive weighs on my mind. I think that when you're doing a Phase 1 study, you know that these things can happen. And I don't think that we helped her quality of life. We've learned something. And I don't know that the family will take heart in the fact that they're part of a legacy of passing the torch to more patients that follow. I hope that that means something to them. But she is a patient who really did not derive benefit and yet taught us something important.
Scott Pelley: You discovered that putting in too much polio virus created too large an immune response.
Dr. Henry Friedman: Absolutely.
And that was the turning point in the daring polio trial. What was learned from Donna Clegg's death may give life to Nancy Justice. Neuro-oncologist Dr. Annick Desjardins cut the potency of Nancy's infusion by 85 percent - it was a lower dose than they had ever intended to use in the study. Even so, Dr. Desjardins expected a big immune response.
Dr. Annick Desjardins: In the next four to six months we should see the inflammations, so the immune system, waking up, starting to kill the tumor.
Scott Pelley: You will expect to see her MRI look worse in the early days?
Dr. Annick Desjardins: Yes, absolutely.
Scott Pelley: Before it gets better.
Dr. Annick Desjardins: Absolutely.
It certainly did. After she returned to Georgia, Nancy's symptoms started to resemble Donna Clegg's -- she had trouble with words, her right side was weak. Her husband Greg took her back to Duke for an emergency MRI. This was Nancy's tumor before the polio infusion, three months later. The site had doubled in size. The swelling had pushed one hemisphere of her brain into the other.
Nurse: Avastin, 500 milligrams.
Dr. Desjardins ordered a small dose of a cancer drug called Avastin, not to treat the tumor, but to reduce the swelling. Nancy's symptoms improved right away and two weeks ago Nancy had a new MRI. It was four and a half months since her polio infusion. And we joined her husband and sons to see the new image for the first time.
Scott Pelley: And you haven't had a chance to see it yet. So, show us, doctor, what you have.
Dr. Annick Desjardins: So, glioblastoma is a tumor that left untreated, you expect the tumor to double in size every two, three weeks. So the fact that we don't see the tumor growing back, we don't see the swelling coming back, we don't see Nancy getting worse, all of that is very positive. It's a sign that the polio virus is doing its job.
On the left is the inflammation that we saw earlier. On the right is the new MRI. Her tumor has a gaping hole. It's being wrecked from the inside out.
Scott Pelley: So where does this go from here?
Dr. Annick Desjardins: So now, we keep following her. And hopefully, it keeps shrinking and it keeps collapsing. And that's what we have seen with Fritz and Stephanie that it continued shrinking for years.
Scott Pelley: Nancy, when you look at this what do you think?
Nancy Justice: Oh, it's amazing. Oh, my gosh. I mean, thank you Lord. And these doctors, thank you doctors. You know, and to just see this-- you know, that's-- that's life. I mean, it's hard to not just start crying.
So far there have been 22 patients in the polio trial. Eleven died. Most of them had the higher dose. But even so they lived months longer than expected. The other 11 continue to improve. Four are past six months which Duke calls "remission."
Dr. Henry Friedman: We clearly are producing a very, very significant benefit. We've got an increase in median survival of over six months, which is huge in glioblastoma.
Scott Pelley: Six months doesn't sound like very much.
Dr. Henry Friedman: I know-- it doesn't sound like much. But that's just-- that's just the midpoint. So we've got patients that are out as far as 33, 34 months. That is just unheard of in this disease.
Dr. Darell Bigner is the head of the study and of Duke's Brain Tumor Center. He's been fighting brain cancer 50 years and he told us he has never seen results like those in patients Fritz Andersen and Stephanie Lipscomb.
Scott Pelley: Based on what you have seen, is it fair to say that Stephanie and Fritz are in remission?
Dr. Darell Bigner: Oh, absolutely. That's probably a very good term to use. They're in remission and I think they would tell you that they consider themselves normal again.
Scott Pelley: Cured?
Dr. Darell Bigner: You know, I'm very reluctant to use the cure word, the C word as we call it because we don't know how long it takes to say that a glioblastoma has been cured. But I am beginning to think a about it.
Dr. Annick Desjardins: Close your eyes. What side am I touching you on?
Nancy Justice: Oh, my left.
But what they've achieved in this rare form of cancer, may be just the beginning. Molecular biologist Matthias Gromeier, the creator of the virus, is pressing ahead.
Scott Pelley: You have been testing this therapy against a number of other cancers just in a laboratory dish.
Dr. Matthias Gromeier: Yes.
Scott Pelley: What have you been able to kill so far?
Dr. Matthias Gromeier: So we have done this for lung cancers, breast cancers, colorectal cancers, prostate cancers, pancreatic cancers, liver cancers, renal cancers. We probably see this in just about any type of cancer you can imagine.
The man who's overseeing the polio trial for the FDA is Dr. Peter Marks, a deputy director responsible for hundreds of other experimental treatments for cancer.
Scott Pelley: You have to wonder if it's too good to be true. Some of the results in these early trials appear nearly miraculous.
Dr. Peter Marks: We hope they really are miraculous. We do have to be cautious because sometimes, people just get lucky. And-- the first patients they treat with a therapy-- respond very well. But subsequently, additional patients don't.
Scott Pelley: Help me put immunotherapy in perspective here. How big an advance is this in terms of viruses to treat cancer?
Dr. Peter Marks: The field of immunotherapy is tremendously exciting. It's been a paradigm shift in how we go about treating cancer. Because there are real products out there that are immunotherapies that are actually helping people to live longer.
Scott Pelley: So we all know about surgery, chemotherapy, and radiation. And now this is a fourth weapon?
Dr. Peter Marks: Yes.
Already 10 drugs that trigger the immune system have been approved and they are significantly extending the lives of patients with cancers including lung cancer and melanoma. According to the rules of the FDA. Dr. Marks couldn't speak with us specifically about the polio trial. But in about a year the FDA is expected to make a decision on whether to grant Duke what's called "breakthrough status" which would make the treatment available to many more patients much sooner.
Glioblastoma kills 12,000 Americans a year. Fritz Andersen expected to be one of them. Before he became the second patient in the Duke trial he wrote his own obituary. He'll have to update it. Three years later, he's cancer free. Stephanie Lipscomb wasn't supposed to see her 22nd birthday.
Stephanie Lipscomb: How are you doing?
Three years later, she's graduated from nursing school.
Scott Pelley: Do you think being a cancer survivor's gonna make you a better nurse?
Stephanie Lipscomb: Oh yeah. It already has. Just because I've been, been a scared patient and so I know and I loved it when nurses held my hand. So I like to be there and be there emotionally for them too.
And as Nancy Justice's tumor continues to shrink, it's now leaving room for her imagination to grow.
Scott Pelley: Nancy, months ago when I met you for the first time, they were dripping the polio virus into your tumor. And you told me about some of the things that you were determined to see in the lives of these boys.
Nancy Justice: Exactly.
Scott Pelley: And I wonder if you're at a place now where you can start making plans.
Nancy Justice: Oh definitely. I mean, that has-- that's been what's keep-- kept me going. I will see them graduate college. I will see them get married. And I will have grandchildren, in that order.
