Chapter 03: New Fields and the Discovery of Vitamin A’s Role in Chemoprevention
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Description
Dr. Hong first describes the trial that demonstrated chemo’s effectiveness for patients of head and neck cancer. (One group was given the standard treatment of surgery and radio therapy and the second treated with chemotherapy and radiation therapy.) Dr. Hong then explains the process by which academic medicine came to recognize medical oncology as a subspecialty. He then explains that many head and neck patients develop second cancers. He defines leukoplakias, the white patches or pre-cancerous lesions that appear in smokers. He explains that he learned about leukoplakias from head and neck surgeons and that these lesions are also associated with Vitamin A deficiencies, a connection that led him to use Vitamin A and its derivatives as chemoprevention agents. Dr. Hong describes the first trials in which patients with leukoplakias were treated with high dose retinoic acid (synthetic Vitamin A) vs. a placebo, yielding a sixty percent response in the former group. This demonstrated for the first time that a chemical treatment could reverse a cancer process. Dr. Hong explains the implications of this discovery as well as how retinoic acid works with cell mechanisms. He also notes that toxicity effects associated with high doses of retinoic acid.
Identifier
HongWK_01_20130916_C03
Publication Date
9-16-2013
Publisher
The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center
City
Houston, Texas
Interview Session
Waun Ki Hong, MD, Oral History Interview, September 16, 2013
Topics Covered
The Interview Subject's Story - Professional Path; The Researcher; Evolution of Career; Discovery and Success; Professional Practice; The Professional at Work; Patients; Patients, Treatment, Survivors; On Research and ResearchersUnderstanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Overview; Definitions, Explanations, Translations; The Clinician
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Disciplines
History of Science, Technology, and Medicine | Oncology | Oral History
Transcript
Waun Ki Hong, MD:
Yeah, it is. So I think, again, I was very lucky. And then I developed a trial. One group gets standard treatment, which is surgery and then radiation treatment. That is the standard treatment, and compared it to chemotherapy and then radiation. So I was the proponentprincipal—this is the Veterans Administration certificate of appreciation. There is a strategy to preserve the human life, and it turns out, the same survival rate.
Tacey Ann Rosolowski, PhD:
Really? But preserving the voice box.
Waun Ki Hong, MD:
Yes, that’s the beauty.
Tacey Ann Rosolowski, PhD:
You know—I was so struck when you said that you were the only person trained as a medical oncologist when you started as a faculty member there. And that—what was that process like of establishing a place for medical oncologists in academic medicine at the time? Was that controversial? It was a new field. What was it like establishing it?
Waun Ki Hong, MD:
It was a new field, but I think that the academic institution at the time had begun to recognize the importance and significance of medical oncology as a subspecialty. Again, you have to be in the right place at the right time. I was in a VA Hospital. Obviously, I was a government employee, and the salary was the lowest one. Then you had to do a lot of things for yourself. Many people, after training, they stayed in the medical school or in private practice. They got more single-scope type jobs. But I ended up to go—and I signed up to be in the VA Hospital. In fact, there is some coincidence, like to catch the tiger and to kill the tiger, you have to go in a cave where tigers live. So—you know—this is a very great coincidence. So I got there, and then I felt some sense of responsibility and obligation to take care of cancer patients, especially about head and neck cancer patients. Then I obtained some drugs in my hand and had an opportunity to conduct a small trial, and I had seen some interesting results. That motivated me to develop a randomized study, and it turns out the same survival. And based on that result and on the trials, related and similar cases became rapidly qualified disseminated worldwide.
Tacey Ann Rosolowski, PhD:
Was it controversial at first?
Waun Ki Hong, MD:
Of course it was controversial.
Tacey Ann Rosolowski, PhD:
Why?
Waun Ki Hong, MD:
Because surgeons were losing their opportunities. When they do a laryngectomy they make money. And then it changed the concept and the culture. At the time there was no one talking about the preservation of the organ. They talked about it, but at the time there was no track record of chemotherapy.
Tacey Ann Rosolowski, PhD:
So you went out to—you were lucky enough to be able to have the cisplatin and then to prove it so people can’t argue with the numbers.
Waun Ki Hong, MD:
Yeah, exactly.
Tacey Ann Rosolowski, PhD:
Well, they can but—now I read somewhere that it was in 1980, while you were at the Veterans Affairs Hospital, that you first heard the term “chemoprevention.” And so that’s a whole really important part of the story.
Waun Ki Hong, MD:
That was at the same time—you know. I had all the cancer patients related with a lot of smoking or smoking and drinking. All the head and neck patients can be treated effectively with surgery or radiation, but many of them come back with a second cancer. Also many patients presented with oral leukoplakia—that is the pre-cancer lesion in invasive cancer.
Tacey Ann Rosolowski, PhD:
Now, I read that leukoplakia translates as “white patch.” So what exactly is that?
Waun Ki Hong, MD:
Well, if you look in the mouth on an area like the tongue or the throat, it’s like a white patch. It’s islands of white patches.
Tacey Ann Rosolowski, PhD:
So that indicates cells that—what has happened to those cells?
Waun Ki Hong, MD:
That’s infected. It’s a pre-cancer cell that produces keratin. This accumulation of keratin is manifested as white patches. Again, there is a coincidence, too. There was something that I learned from head and neck surgeons. I didn’t know that until they taught me. This is a pre-cancerous lesion, oral leukoplakia. That is also associated with some vitamin A deficiency. And some pre-clinical studies show some vitamin A compound or synthetic vitamin A is capable of reversing a process.
Tacey Ann Rosolowski, PhD:
Because I was going to ask you where you got the idea to use retinoids to treat it.
Waun Ki Hong, MD:
That was some pre-clinical work and then some publications. Then, again, I’m a very lucky person. Then I was supposed to buy help from La Roche, and they had a drug at the time that was synthetic vitamin A, cis retinoic acid. And then some people used that thing in lozenge form.
Tacey Ann Rosolowski, PhD:
I’m sorry.
Waun Ki Hong, MD:
Lozenges.
Tacey Ann Rosolowski, PhD:
Oh, lozenges.
Waun Ki Hong, MD:
And they had seen some dramatic response. And then they manufactured pills, and I had the opportunity to develop obtain the drug.
Tacey Ann Rosolowski, PhD:
So this was prior to your coming to MD Anderson?
Waun Ki Hong, MD:
Right.
Tacey Ann Rosolowski, PhD:
So tell me about the first trials that you did with that.
Waun Ki Hong, MD:
The individuals presented with oral leukoplakia and then were treated with high dose retinoic acid and compared to placebo. And it was a dramatic response, like a sixty percent response in the retinoid group versus about ten percent placebo. It was an exciting discovery. That’s the first time that a chemical treatment can really reverse the process. What that means—reversing the process means that it has the potential to prevent the cancer.
Tacey Ann Rosolowski, PhD:
So what chemically happened in the cells?
Waun Ki Hong, MD:
Obviously, the pre-cancer cell shows some inability for differentiation. Okay, and also once a rapid differentiation takes place, then in all the cells it can be proliferated. And the retinoic acid can induce normal differentiation and turn the cell back into normal behavior. It’s a simple strategy. Then the cell proliferation can be regulated. Like you see bad apples actors on the street and they can kill people. But from the bad apples actors being identified, you can prevent the crime. Retinoic acid can really moderate modulate the cell behavior.
Tacey Ann Rosolowski, PhD:
That’s amazing.
Waun Ki Hong, MD:
It is. That’s the good news. The bad news is that there is toxicity.
Tacey Ann Rosolowski, PhD:
Okay. So tell me about that.
Waun Ki Hong, MD:
Really people who take high-dose retinoic acid—if you offer it to friends, it will break up the relationship. It makes your life miserable.
Tacey Ann Rosolowski, PhD:
So when we’re talking about a toxic lever, or when we’re talking about a high dose, how high is that dose? What is the dosage?
Waun Ki Hong, MD:
That drug has been used for treatment of acne. It’s a similar dose.
Tacey Ann Rosolowski, PhD:
And what is the dose? I’m not aware.
Waun Ki Hong, MD:
About two milligrams per kilo.
Tacey Ann Rosolowski, PhD:
About two milligrams per kilo. And that’s considered a toxic dose?
Waun Ki Hong, MD:
Yeah.
Tacey Ann Rosolowski, PhD:
How long do you have to take it before it becomes dangerous to you?
Waun Ki Hong, MD:
You can see the biology biologic effect affected in three to six months. And long-term treatment—there is some problems with that. Problems with the skin toxicity, eye toxicity and bone toxicity.
Tacey Ann Rosolowski, PhD:
So what happens when a person is going toxic with vitamin A?
Waun Ki Hong, MD:
Life can be miserable.
Tacey Ann Rosolowski, PhD:
Okay.
Waun Ki Hong, MD:
The cancer course can be reversed, but other qualities of life can be really affected.
Tacey Ann Rosolowski, PhD:
What are the symptoms?
Waun Ki Hong, MD:
Dry skin, cheilitis, and also the lipid level—hypertriglyceridemia. I think that is the downside. But that’s the first evidence that a chemical drug can really reverse the process of carcinogenesis.
Tacey Ann Rosolowski, PhD:
Now was that a very new idea about cancer? I mean, at the time when you—
Waun Ki Hong, MD:
Fairly new idea.
Tacey Ann Rosolowski, PhD:
That you could actually reverse it?
Waun Ki Hong, MD:
Yeah, but I was not the first one to talk about it. I was lucky to have the drugs and patients there. But clinically it was the first time that demonstrated that, yes.
Tacey Ann Rosolowski, PhD:
And so what year did you publish those results?
Waun Ki Hong, MD:
I think that was 1986.
Recommended Citation
Hong, Waun Ki PhD and Rosolowski, Tacey A. PhD, "Chapter 03: New Fields and the Discovery of Vitamin A’s Role in Chemoprevention" (2013). Interview Chapters. 1096.
https://openworks.mdanderson.org/mchv_interviewchapters/1096
Conditions Governing Access
Open
