Chapter 09: NIH Fellowship: Researching Drugs with Amazing Effects on Patients


Chapter 09: NIH Fellowship: Researching Drugs with Amazing Effects on Patients



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In this chapter, Dr. Benjamin talks about his work with anthracyclines and daunorubicin at the Baltimore Cancer Research Center. Dr. Benjamin determined the pharmacology of the recently introduced drug, Adriamycin. He describes the protocol and comments on the policies regarding consent forms at that time and now. He then talks about the results, which showed that Adriamycin was the most active drug in solid tumors up to that point. He tells a very dramatic story of the effects on a patient with metastatic sarcoma (Dr. Benjamin's first sarcoma patient). Dr. Benjamin next explains that he became involved studying the pharmacology of cancer drugs and that no one had really done that before. He stayed an extra year on this fellowship to continue his studies. He explains changes in credentialing rules that resulted in his time with the NIH to satisfy the requirements for both Internal Medicine and Oncology.



Publication Date



Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; Professional Path; Character, Values, Beliefs, Talents; Evolution of Career; Professional Practice; The Professional at Work; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Inspirations to Practice Science/Medicine; Influences from People and Life Experiences; Discovery and Success; Human Stories; Offering Care, Compassion, Help; Patients; Cancer and Disease; Formative Experiences; Patients, Treatment, Survivors


Tacey Ann Rosolowski, PhD:

Wow. So what were the—

Robert Benjamin, MD:

And then I got into my second year of this program, started working in the laboratory, and I worked with a wonderful boss, Nick Bachur.

Tacey Ann Rosolowski, PhD:

I’m sorry, his name?

Robert Benjamin, MD:

Nick, Nicholas Bachur, B-a-c-h-u-r. And Nick was a quiet guy. He worked completely in the laboratory, never saw patients there. He was the laboratory scientist in a sense, but MD, not PhD. He was interested in studying the anthracycline antibiotics. We used Daunorubicin extensively in the treatment of leukemia, and it was a reasonably new drug during some of that period of time but a few years before I got there, and it had become established as one of the main drugs used to treat leukemia. And Nick had performed the original clinical pharmacology studies of that drug with another one of the clinical associates who was a year ahead of me, and I helped them a little bit with that, but it was primarily their studies on Daunorubicin.Around that time, the Italians had introduced a drug called Adriamycin into oncology, and it had not been used at the NCI before. So Nick thought that the methodology that he’d used to study Daunorubicin would be applicable to Adriamycin, so that we should do a study and study the clinical pharmacology of Adriamycin because although it had been used previously, there was no information on the pharmacology, or what was there was probably wrong because of methodological aspects. So my job as a clinical associate was to study the clinical pharmacology of Adriamycin. So Nick said, “Write up a protocol to give Adriamycin to these patients, and let’s study the clinical pharmacology, and you can do both aspects.”So I went to Peter Wernick [phonetic], who was this former clinical associate there who had gone for oncology fellowship at Hopkins and now came back to lead the clinical program during my second year. So I said to him, “Nick wants to study the clinical pharmacology of Adriamycin.”And he looked at me and said, “You know, it’s an analog, Bob. Analogs never work any better than the parent compound. It’s sort of not important. But you want to study the pharmacology, that’s fine. We can certainly find a few patients. How long will it take you to do a patient?”I said, “Well, probably about a week, because we’ve got to get the drug. I’ve got to collect the samples for three days. It’s going to take me a couple days in the lab to analyze them. So probably a week for a patient.”And Peter thought and said, “Yeah, sure. Go ahead. Write a protocol.”So I wrote a protocol. And Nick had said to me, “Make sure that in the protocol you specify that you want to study not only patients with carcinoma, but sarcoma, because the Italians reported some responses in patients with sarcomas, and I don’t remember ever seeing a drug that works on sarcomas. So it might be interesting to get some patients like that.”So I said, “Sure.” So I wrote this protocol to give Adriamycin, and I included patients with sarcomas, and I got the drug. There were actually some patients in the Public Health Service Hospital that weren’t BCRC patients, they were just hospital patients, but there were some patients who were there who had cancer that they weren’t really doing anything for. So they allowed me to include some of those patients on the study as well, as long as they agreed. And informed consent then was very easy. You walked up to them and said, “I want to try this new drug. I’m going to give it to you. I’m going to take all these blood samples, analyze it in the lab, see what happens to the drug, see what happens to you. Is that okay?”And they say, “Yeah, sure.” And that was your informed consent. Probably a lot better than the informed consent that we have now, which is so long and so complicated that nobody pays any attention to it, except that they, “You have to sign this form to get on the study.”“Okay, Doc.”So Adriamycin turned out to be the most active drug in solid tumors that had been introduced up until that point in time. The second patient that I treated on the study was a patient with metastatic sarcoma, and his name was $$Elmer Wheatley [phonetic]. Elmer was one of these Public Health Service Hospital patients that wasn’t a BCRC patient, and he had been in the hospital for two weeks and he was bedridden. He never would qualify for a protocol in our current studies because his performance status was four, his life expectancy was probably two weeks, but back then we didn’t care about those things. He was getting injections of morphine pretty much around the clock and it really wasn’t controlling his pain. Probably he didn’t get enough morphine, but that’s back then. I guess we weren’t so good at treating pain either.But I went and saw him, and because I was drawing all of these blood samples like every fifteen minutes for the first hour and then every half an hour and then every hour and then every two and four and whatever, I kept seeing him multiple times during the period. And probably by about my four-hour sample, he looked at me and he said, “You know, Doc, I think I’m feeling better.”And I said, “Gee, that’s great,” and I thought to myself, wow, placebo effect is really striking, isn’t it. By the time I got the twenty-four-hour sample the next day, he was sitting up in the bed. He hadn’t been sitting up in the past two weeks. When I drew my seventy-two-hour sample, which was the end of the study, he got up and walked out of the hospital, and came back to see me in the clinic a few weeks later, and he actually ended up living for about eight months. We didn’t have anything else to treat him with. But it was truly remarkable.Before I had started him on the study, I had to present his case to Peter Wernick, because he was the clinical boss and he was in charge of all of this stuff. He said to me—his description of this guy was, “Well, I hope he lasts long enough for you to get all your samples, because he has one foot in the grave and the other on a banana peel.” And he lived eight months. So that’s my first sarcoma patient.So Adriamycin turned out to be a really important drug. I totally lucked out by getting that drug to study, and I got involved with studying Adriamycin and doing clinical pharmacology on chemotherapy drugs, and nobody had really done that before. Nick Bachur’s studies were sort of pioneering in that aspect.So I ended up staying an extra year at the NCI because my studies were going well. I didn’t want to stop in the middle, and they let me stay on as a—I don’t know, whatever their title was, for an extra year. So I spent three years there instead of two. During that third year, the American Board of Internal Medicine changed its rulings about what was a formal oncology fellowship, and anyone who had been at the NCI at the Cancer Center was considered to have gone through an oncology fellowship. So if I’d left after two years, I would have gone somewhere else and done a two-year oncology fellowship. By staying the extra year, I actually satisfied all of my requirements for internal medicine and oncology and came out board-eligible for medicine and oncology at the end of the three years at NCI. So I had very little formal training but—

Tacey Ann Rosolowski, PhD:

But clearly a lot of luck. (laughter)

Robert Benjamin, MD:

A lot of luck.

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Chapter 09: NIH Fellowship: Researching Drugs with Amazing Effects on Patients