The Uromigos Episode 122: Legends in GU Cancer Series—Nick Vogelzang and Renal Cancer

Dr. Nick Bogelzang discusses his career and describes treatment advances in RCC.

Episode Transcript

Tom:
Hi, everybody. This is the … of a podcast named The Legends. We’re getting legends from oncology together. Some legends are keen to take part, others are nervous. Some, frankly, refused.

That’s not true, no one’s refused yet. We’re super excited to be joined here by our first legend, Nick Vogelzang who, Nick … yourself in a second. I know you and Brian go back a long way, and we’re really excited to have you on. Thanks for coming.

Nick Vogelzang:
Oh, you’re welcome. I’m enjoying the view over my golf course view, looking at the desert, the palm trees, and the sand and the desert view. So, thanks for having me on.

Brian:
Do you want to introduce yourself briefly, Nick?

Nick Vogelzang:
Yeah. Yeah. I was a Midwest boy from Michigan raised in Holland, Michigan, 10 generations of Dutchmen. Grandfather migrated to the cold, windy, snowy Grand Rapids, Holland, Michigan. I caught the research bug when I was in college, working at Argonne National Laboratory.

And pretty soon before I knew it, I was working at University of Chicago and delving into the wonders of science, and I never quite gave it up. Ended up following that bug for my first 25 years at University of Chicago, and then came to Nevada to hopefully start a research project here, but the state ran out of money during the downturn of the 2018, 2009 recession.

And I ended up migrating into a private practice and didn’t want to move my family back into another environment when they’d already started high school, so I stayed in private practice for the last 15 years and I’ve enjoyed it thoroughly taking care of patients.

Tom:
Nick, do you see yourself first as a researcher or a doctor?

Nick Vogelzang:
Both, I love patients …

Tom:
Got to pick one, Nick, got to pick one.

Nick Vogelzang:
Oh no, no. I’m primarily a doctor, who happens, on the side, to do research.

Tom:
Nick, when you started your career, did you know that [inaudible 00:02:58] as a doctor, or did you stumble across research as something that was interesting? And why was it cancer and not [inaudible 00:03:03] disease?

Nick Vogelzang:
I came from a long line of people who served others. My mother was a teacher, my dad was a pastor, and the family always wanted me to be a doctor, but I absolutely adored the science behind medicine and that …

My dad even wanted me to be a missionary and that was too much service. And so, when I went in to do my internship and residency, the idea was that I would serve in the community, and I couldn’t find that to be acceptable either. So, I ended up staying in more of an academic hybrid model.

Brian:
Nick, talk about, a lot of the listeners know that you were my original mentor and I think you’ve mentored probably dozens, if not more GU oncologists and probably other oncologists as well.

Talk about some of your early career influences. Because I think you were in sort of one of the first waves of oncologists, so talk about the people who sort of helped you take those first career steps.

Nick Vogelzang:
Yeah. So, when I was at Rush, Rush medical school was a very old medical school. One of the first in the United States who was founded in 1842 and was, I think the first in Chicago and probably one of the first of the 10 or 20 medical schools in the United States.

So, their goal was always to provide medical care to the south side, west side of Chicago, a traditionally underserved community, many medical school students were Black, actually.

I migrated to that side of the care. It was always meant to be a caring medical school. And I just love teaching, and my first training program was in Minnesota, and I ended up with a fellow by the name of BJ Kennedy who was one of the ASCO presidents.

And he had an interest in testicular cancer and that’s how I ended up teaching about testicular cancer. I was then offered through the good graces of Clara Bloomfield, another person who is a rockstar in oncology and hematology, opportunity to go to her alma mater at University of Chicago and stayed there for 24 years.

I had some amazing medical students, one of whom was Brian [Rini 00:05:57]. Walt [Statler 00:05:57] was there.

Tom:
Now Walt was successful.

Nick Vogelzang:
Yeah, there were a few stars there.

Tom:
Nick, I’ve got a couple of questions. So, the first is, did you stumble into cancer and did you start … Did you always know you were going to do cancer? And what was the environment like at the beginning? Because my first ASCO had 20,000 people in massive sort of aircraft hangers, I’m guessing things were different when you started.

Nick Vogelzang:
No, when I was accepted in medical school, I had the great fortune to be given a full research program. I was a James Scholar, and that meant that I didn’t have to go to classes, and instead I spent almost the good part of my first three years of medical school hanging out at the laboratory and basically tinkering. And we spent time looking at the herpes virus and its ability to cause cancer, and I made many a poor mouse ill from cancer.

And so, when I got into my internship, I didn’t really know much about medicine, but I knew a whole lot about cancer. And so, when I first saw patients with cancer, I was going, “Oh my God, they must have a viral-induced cancer.” And of course, that wasn’t true, most of them were carcinogen-induced, but I was totally enthralled when some of my faculty members who’d trained at Sloan Kettering started giving chemotherapy. And lo and behold, the cancers disappeared.

Doxorubicin and cisplatin were just coming on the market and just were available, and golly, I was totally enthralled. And then when that wonderful drug cisplatin became available in 1974, during my internship, I said, “I got to give this drug.”

And I started giving it and cancers started to melt away. So, by the time I was done with my residency in ’78, Dr. Einhorn’s papers came out and I said, “Sign me up. I want to do this.”

Brian:
And Nick, you did a lot of chemotherapy drug development across malignancies, right? That’s my recollection from residency.

Nick Vogelzang:
That’s right. Yes.

Brian:
A lot of phase one work. Mesothelioma, kidney and prostate, and the lot. Take us back to those days, what was that like? Because you didn’t have targeted therapy and immune therapy and all of these different molecular subsets. It was chemo drug A, B and C.

Nick Vogelzang:
We were fortunate that the NCI at that time had a broad drug development. There were no pharmaceutical companies, you had Bristol, and Bristol of course had platinum and bleomycin and vinblastine, and that was the drug powerhouse.

The NCI had a very robust drug development program, so we were just literally handed drugs to develop. And we were … neocarzinostatin and all these weird drugs. And we were told, here, do broad phase two studies.

And then gradually other drug companies came on the market, Lilly and so on, and we seized these things. Dan [Von Hoff 00:09:28] being an NCI guy. And he would say, “Let’s try this drug in this disease.” And it was the drug versus bug theory. And you would just do whatever came along.

I happen to have a lot of interest since my days at Minnesota of mesothelioma. And I got to study mesothelioma, but when I walked into the halls of University of Chicago, no one was doing kidney cancer.

There was literally no one in the entire city of Chicago, four million people, doing kidney cancer. I corralled Walt Statler into doing kidney cancer with me and Mark [Retain 00:10:09], I got him to do phase one with vinblastine and how to give it better. And Rich [Schilsky 00:10:18] doing GI cancers. It was just, it was like a kid in a candy store doing new drugs and new bugs.

Tom:
Nick, when you look back at kidney cancer, what for you were the key milestones in drug development in kidney cancer? Do you want to have a go at that?

Nick Vogelzang:
Sure. So, when I got to University of Chicago, Harvey Golomb was doing interferon for hairy cell leukemia and George [Cassata 00:10:57] and MD Anderson had reported that a few patients had responded to interferon. And that was interesting.

And so, the NCI gave us beta interferon and gamma interferon to test. Didn’t see much activity. We saw some very interesting toxicity with beta interferon, and we did some studies with gamma interferon, and didn’t really see much.

And then we had the reports from Dave Parkinson of interleukin-2, high dose interleukin-2. And so, we ran down that path of beta alpha interferon plus interleukin-2. And so, we … And Brian got involved in the interleukin-2 high dose plus interferon.

And then we had the interesting data of high dose chemotherapy and stem cell transplant with immune reconstitution. And we thought, well, maybe that might work.

Tom:
Nick, at this point, when you were developing these drugs, did you look back at other tumor types and think, why are we getting it so wrong? Or do you think that you were making adequate progress? In the knowledge that Brian was on your team at this point. Did you think about changing the team at any point?

Nick Vogelzang:
Well, it was sort of like a desert. As I look out at the desert here, it was like, what is growing in the desert? We saw a few hints of activity, and we tried to find out why it was working. You were grasping, to some extent, at straws. And we were fortunate to have a robust phase one program.

I remember when we got the first phase one going of sorafenib and our very first patient was a former NBA basketball player with a brainstem metastatic renal cell carcinoma. And he, for some reason, was able to get on sorafenib. And four months later, he was still alive and had a regression and it was Walt Statler’s patient. And we all said, holy mackerel, he’s still alive.

And the tumor had shrunk. And that was what led us to believe that sorafenib had activity. And sure enough, we kept going and that led sorafenib and then Ron [Bukowski 00:13:38] picked it up and Bayer got a drug out of it.

Brian:
Nick, talk about that. Because that was basically right as I was in fellowship and there was a lot of gemcitabine, 5-FU, et cetera, all the, like you say, just sort of wandering in the desert. And you’d see a response here or there and get excited, but then you’d treat more patients, and nothing happened.

But then when our first VEGF targeted therapy came along with sorafenib, it was pretty clear something was different, right?

Nick Vogelzang:
Yeah. We had from 1991 through 2005 wandered in the desert, finding little glimpses of activity with gemcitabine and 5-FU and interleukin, interferon. And then suddenly we saw consistent activity of sorafenib, and we tried to try to say, are we just seeing a mirage in the desert or are we really seeing activity? And consistent activity was seen with sorafenib.

And at the same time, the sunitinib was found to be active. And it was a true eureka moment. Without hyperbole, that was a breakthrough. 2004, 2005. It blew away all of our work with interleukin-2 and interleukin … all the interleukins. Cytokines have come back obviously, but the gemcitabine, 5-FU, although there was clear-cut low-level activity, it didn’t stand up to the TKI therapy. It just didn’t.

Tom:
Nick, how did the … When do you remember the first immune checkpoint excitement, and how did that compare to the VEGF targeted therapy excitement?

Nick Vogelzang:
Oh, the checkpoint activity was of a magnitude above the TKI because we were struggling with TKIs and what do you do when they’re resistant? We were looking at TKI one and then TKI two and TKI three, and suddenly Bob [Motzer 00:16:02] and others saw this amazing response in third-line.

And I remember we thought, well, look, cabazitaxel, [Monte Paul 00:16:13] was finding activity and Tony [inaudible 00:16:16] saw activity with cabazitaxel and the met pathway. And we all said, good, good. We got something here.

And then all of a sudden, we had the checkpoint inhibitor with nivolumab, and it worked. And again, another eureka moment. And it was better than sorafenib and it was able to rescue patients. And so, we knew that this was a mechanism that was superior to TKI, and when it was able to beat [inaudible 00:16:55] and then it was able to beat the TKI upfront, now we see the combination nivolumab ipilimumab.

And by the way, I can’t speak formally about this, but we’re looking at a big study looking at [crosstalk 00:17:12].

Tom:
Let’s avoid stuff we can’t talk about. We are going to broadcast for this.

Nick Vogelzang:
Yeah. Oh, that’s right. I won’t say it then, but in US Oncology we’re looking at nivo/ipi versus pembro/axi, and Brian’s going to be happy with this. It looks like pembro/axi is actually a better combo than nivo/ipi.

Tom:
We don’t know the answer.

Brian:
Controversial statements.

Nick Vogelzang:
But I won’t say that in public.

Brian:
Nobody listens anyway. Don’t worry.

Tom:
Nick, having taken that with a pinch of salt, which we have …

Nick Vogelzang:
Yeah, take it, please.

Tom:
I guess the next bit is around, why have we been so poor at developing biomarkers in kidney cancer? What went wrong?

Nick Vogelzang:
I think the problem was that there were no circulating biomarkers that could be assayed. And it was not that there was no circulating cell-free DNA, but the technology just didn’t catch up. There was no technology that we could use. And that’s why I was …

You got to remember, I’m a biomarker guy from AFP HCG LDH days, and I’ve always loved biomarkers.

I do PSAs like crazy. And there was no technology like that for kidney cancer. And even today, there’s no technology like that. And we want that. We need that. But when that is available, just like now there’s cell-free DNA for bladder cancer, it will take the field by storm. All we need is that simple biomarker blood test.

Brian:
Nick, I want to go in a little different direction. You were one of the founders of the Kidney Cancer Association, KCA. Take us back to those early days. And I don’t even remember the year, but I remember going to some of the first meetings when I was a fellow. So, take us back.

How did that start? How have that organization and similar organizations grown, and what are their role now in the disease?

Nick Vogelzang:
Yeah, it was really pretty simple. I was patterned after the S2 prostate cancer group that was patterned after the Y-ME breast cancer group. I had a lot of patients back in the early and mid-eighties, many of them from South Bend, Indiana and Fort Wayne, Indiana.

It wasn’t a very creative thing, but I realized the need to have patients involved in their own life decisions and to give them an opportunity to communicate.

And there was no HIPAA back then, but they were dribbling in one at a time. And I said, “You guys should talk to one another.” So, we put together meetings in our group at University of Chicago. There had been a small attempt at UCLA to do the similar and one small attempt at Cleveland Clinic to do the same. And I guess I was just a little bit more pushy about doing it.

We put together about 30 patients, two or three months in a row. We got my ex-wife at the time, Jean, was a lawyer and we put together a formal constitution and all that.

Got constituted in a really dynamic … a double PhD from Northwestern. Gene Schoenfeld joined the fourth meeting, and he got the thing started and got Northwestern patients involved. And before you knew it, we were off and running and had a formal group called the KCA. And we got a letterhead and started meeting at neutral sites.

Because the Northwestern people didn’t want to come down to the University of Chicago, and the University of Chicago people didn’t mind traveling up a little to nicer restaurants.

Tom:
Nick, what’s the role of the KCA moving forwards?

Nick Vogelzang:
Well, it’s about 30 to 40,000 mailing list. They got a nest egg of about 26 million. They’re running meetings all around the world and they’re funding research now. They’ve got about a three to $4 million a year research budget. They have peer-reviewed projects all around the world.

Our founding director left the scene. He was sort of iron fisted. Good for the group at the time, built a good nest egg.

Now we have, the group is formally at MD Anderson or near MD Anderson. Chris Wood is a surgeon. He’s the leader now. And we have our official executive director who’s charming and wonderful and makes it all happen. We’ve got a full staff. So, I think it’s on a strong footing.

We have no reason to think that the board is anything but solidly in place and committed to making this a worldwide organization.

Brian:
Nick, I want to talk a little bit more about your career. So, what was that one moment or publication that was more impactful than you thought? Or something you did that you look back on, maybe it’s a big publication, maybe it’s not, that you say, man, that’s something that I’m really proud of?

Nick Vogelzang:
Yeah. I looked at that not long ago. It’s funny. You go to Google Scholar, and what I’m credited for interestingly was a paper I wrote during my fellowship about Raynaud’s phenomenon toxicity from testicular cancer. I spent a lot of time at it.

I dissected the arteries of a guy who died of testicular cancer and found out that bleomycin damaged his hand arteries and got the paper published in the annals of internal medicine against the negative publicity from Larry Einhorn.

And now it’s commonly known that bleomycin is an arterial toxic drug, and it’s widely known now that bleomycin should be given with care. And we only give it nine doses for that very reason in the BEP regimen. And even now it’s still quoted as a sentinel paper for nine doses of bleomycin.

The other big one of course was the, interestingly not GU paper. That’s the mesothelioma paper of Alimta and platinum because Dan Von Hoff and I had noodled about when to give that drug Alimta, and he said, “Well we only give platinum, why don’t we just add that Alimta to platinum?” And the doublet combination was better than singlet. It was a plenary at ASCO.

Tom:
Nick, a question. Is the academic community in kidney cancer going in the right direction?

Nick Vogelzang:
I think that the bravery that we had in the 2000s with TKI is not so prevalent. I think we need a little bravery and boldness and I …

Tom:
What does that look like?

Brian:
Do you mean trial designs? Or drugs?

Nick Vogelzang:
I think trial design needs bravery. And there’s a temptation to follow the money that is very abundant from pharmaceutical companies, but there is also a need to be courageous and decide what are the most important studies.

And I heard Brian the other day say, “Look, we know that all these doublet regimens work, and they probably are equally good, but what we really need are biomarker-informed trial designs.”

Tom:
I think it was me who said that actually.

Nick Vogelzang:
Was it, Tom?

Tom:
No, I’m only joking.

Brian:
Give me a break. Come on.

Nick Vogelzang:
Sorry, Tom. I didn’t mean …

Brian:
It was definitely not him.

Tom:
No, I’m only messing around, Nick. I’m only messing around.

Nick Vogelzang:
But Brian is correct. We need biomarker informed designs, but those are not lucrative. Those are hard trials to write and hard to run. And there’s not a consensus yet as to what is the right design. And right now, we need tissues to help design those, and the IDMC stratifications still are fuzzy. And so, getting an intermediate risk group will give you blurred edges.

Brian:
Yeah, agreed.

Nick Vogelzang:
And how is a genomically designed trial going to move the field is a real question. So, I’m not sure.

Tom:
Nick, did Elvis have any impact on your move to Las Vegas?

Nick Vogelzang:
When I left University of Chicago, I was given a pair of blue suede shoes and a rattlesnake. But no, the only influence that Elvis had on moving to Las Vegas was they doubled my salary to come to Las Vegas.

Tom:
Nick, I’m aware of many aspects of your work, but I’m very aware of your work with US Oncology. Is that something that’s transitioned from when you moved from north to south?

Nick Vogelzang:
It didn’t. I’ve moved a little bit away from US Oncology because US Oncology is a gigantic business. I don’t follow US Oncology as much as I did when I first got here, because I’ve become much more independent, frankly. I’ve begun to create, if you will, my own weather.

Many of the pharmaceutical companies now come to us and me and my team here, more or less independently of US Oncology. It’s sort of gratifying. And so, we get to pick and choose among the companies that we want. Like yesterday, I got a couple of calls from small companies. I got an email from Abbott about a new met-directed therapy, combining a met antibody against …

Tom:
[crosstalk 00:29:05].

Nick Vogelzang:
Yeah. Just fun.

Brian:
So, let’s do it, Tom. Let’s go into speed round. Nick, I don’t know if we warned you. There’s a speed round at the end of these.

Nick Vogelzang:
Yeah, speed round.

Brian:
We’re going to rapid fire questions.

Nick Vogelzang:
Go. Go.

Brian:
All right, Tom, you want me to start?

Tom:
Yes, you start, Brian.

Brian:
Year and subject matter of your very first publication.

Nick Vogelzang:
Alosa pseudoharengus, the Lake Michigan alewife. Boy. What year? 1978.

Brian:
Awesome.

Nick Vogelzang:
Maybe.

Brian:
Tom, you go.

Tom:
Neil Diamond or Neil Armstrong?

Nick Vogelzang:
Oh, you stumped me. I don’t know.

Brian:
You have to pick one or the other.

Tom:
You have to pick one, Nick.

Brian:
There’s no wrong answer here.

Nick Vogelzang:
Neil Diamond.

Brian:
Excellent. How many publications do you and I have together? What’s the number of publications that we’d been co-authors?

Nick Vogelzang:
I think about 20 plus, maybe 22 or 23.

Brian:
I think that’s close. I searched PubMed. I thought it was 17, but in the ballpark.

Nick Vogelzang:
Yeah, you were one of my most prolific co-authors.

Brian:
I wasn’t searching for a compliment.

Tom:
It went downhill after he left you, Nick.

Nick Vogelzang:
It’s ranked self-proliferation, Brian. You’re just a prolific author.

Brian:
Thank you, Nick.

Tom:
Nick, favorite Olympic sport.

Nick Vogelzang:
I’ll have to give a nod to my beautiful wife who’s an Olympian horse promoter. So, she loves all things horsey.

Tom:
That’s a good shout out.

Brian:
Favorite place you’ve ever been invited to give a talk in the world.

Nick Vogelzang:
Oh, Istanbul.

Brian:
Ooh, excellent.

Tom:
James Bond or Lara Croft?

Nick Vogelzang:
Oh, James Bond. Oh, James Bond for sure.

Tom:
Last question.

Brian:
Most embarrassing publication.

Nick Vogelzang:
Neocarzinostatin.

Tom:
What happened with that, Nick?

Nick Vogelzang:
A dead-end drug for sure.

Brian:
I’ve never even heard of that drug. So that’s good.

Tom:
Nick, this has been fantastic. We’ve really enjoyed having you on. You’ve not been on before. We hope we can grab you in the future and get you back with us. It’s been really enlightening. Thanks so much for your time today.

Nick Vogelzang:
My pleasure guys. Thanks for doing this. It’s really an honor. Really, really an honor. I appreciate all your time.

Brian:
Put it on your CV. Feel free.

Nick Vogelzang:
I will.