Chapter 08: Early Clinical Studies
Files
Loading...
Description
Dr. Cox begins the discussion of his research career with his residency. He explains that hypotheses in clinical research derive from the care of patients. Survival is the “immutable endpoint” that determines whether a treatment is successful, but survival does not tell you why a treatment is successful. Early in his career, Dr. Cox developed an approach to determine why treatments succeed, though he observes that many of the questions he asks about patterns of failure are irrelevant from other perspectives (e.g. medical oncology).
Dr. Cox describes studies done in the 70s with lung cancer to determine why treatments failed. When he became involved in the Radiation Therapy Oncology Group (RTOG) his style of designing studies influenced the group. All of the ROTG studies during his ten years with the group used survival as the endpoint. Returning to his residency years, Dr. Cox talks about his studies of cancer of the breast and cervix. Dr. Cox notes that his view of clinical trials was strongly influenced by his mentor, Dr. Juan del Regato.
Identifier
CoxJ_02_20130412_C08
Publication Date
4-12-2013
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Researcher; The Researcher; Overview; Definitions, Explanations, Translations; MD Anderson Culture; On Research and Researchers; Understanding Cancer, the History of Science, Cancer Research; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Patients, Treatment, Survivors; Healing, Hope, and the Promise of Research; On Research and Researchers
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
Tacey Ann Rosolowski, PhD:
This is Tacey Ann Rosolowski, and today I’m at the Proton Therapy Center in the office of Dr. James Cox, and we’re in our second session. The time is about 11:25, and the date is April 12, 2013. So thank you Dr. Cox for agreeing to do this session. We were strategizing before I turned on the recorder and decided that today would be a good day to devote to the discussion of the research that you have done. I’m hoping that we can go back to fairly early—the research that you first conducted when you first came to MD Anderson and even if there’s a relevance in tracing the roots of that in your previous positions and tracing the evolution of that research career and story.
Tacey Ann Rosolowski, PhD:
We were strategizing before I turned on the recorder and decided that today would be a good day to devote to the discussion of the research that you have done. I’m hoping that we can go back to fairly early—the research that you first conducted when you first came to MD Anderson and even if there’s a relevance in tracing the roots of that in your previous positions and tracing the evolution of that research
James D. Cox, MD:
Well it starts back as early as my residency, and it is all clinical research. Now a side comment about clinical research is that it is not very highly respected academically.
Tacey Ann Rosolowski, PhD:
Yeah, you were talking about the last time we spoke.
James D. Cox, MD:
So for somebody to spend a career doing that, you could say, “Well, that’s a lot of wasted time.” And it is if you look at it from the point of view of a basic scientist, where to design a discrete experiment in the laboratory, carry it out over a period of weeks or months or maybe a couple years, and then have a paper to write or more papers to write because the research has been based on a specific hypothesis. Now in clinical research, I think the hypothesis derives, at least to a considerable degree, from the care of patients. And I think in caring for patients, one comes up against questions that are not adequately answered. One can develop a hypothesis about what that might be.
Tacey Ann Rosolowski, PhD:
Can you give me an example?
James D. Cox, MD:
Well an example that goes back far but also comes to the present time is when people do clinical trials, the ultimate endpoint is survival. And that is an immutable endpoint. Nobody can argue with being alive or dead. Any of the other endpoints are less crisp, I guess—they’re not as definitive. Well that tells you whether you have been successful in a certain kind of treatment, but it doesn’t tell you anything about why. And so early on I developed an approach that said, “Okay. If we’re failing in treatment, why are we failing? Is it because we have not eradicated the local tumor? Is it because if we were treating with radiation therapy, we have not had a large enough field so the tumor’s recurred at the margin of the field that we treated? Or the tumor has spread.” Now in some quarters—and I think this is true in much of medical oncology—those questions are immaterial because their paradigm for the treatment of cancer is leukemia, which is disseminated from the very beginning. And so they don’t find it very useful to ask about patterns of failure. But I’ve been doing that all of my career, and I can continue to be doing that with the proton effort now. We’ve uncovered some interesting things. If you fail to eradicate the local tumor, is it because the dose—I’m talking now entirely about radiation therapy—is it because the dose was not enough? Or was there uncertainty in the dose distribution? And of course disseminated disease speaks for itself. Well I started to this with cancer of the lung in the 1970s.
Tacey Ann Rosolowski, PhD:
What prompted you to begin asking questions in that way?
James D. Cox, MD:
It was, in part, my training. It was, in part, the discussions with Dr. del Regado, my mentor. He didn’t frame it in the way that I just did, but he did ask, “Why did we fail?” And that’s an important question. It’s an important question for anybody that’s dealing with local treatment. It would be a similarly important question for a surgeon who’s trying to remove a tumor and ideally remove it all. Or the sidelight of it is the consequences of treatment, the toxicity, the functional deficits. So that’s another side of the treatment equation. And so having an approach to that—as far as research strategies are concerned—when I became involved with the Radiation Therapy Oncology Group in the very late 1970s, I brought those questions to the group, and over time that helped color some of the research that went on with the group. Although all of the phase three studies that were designed at the time when I led the group during that ten-year period, all of them had survival as the endpoint. Now that is not true at the present time. It’s not true in studies that are being done here, but still I contend that it’s the ultimate endpoint. Still it doesn’t give you the answer of why you succeed or fail. And you’re happy to succeed so you pass that off, but if you fail, there’s a reason. And as time went on, I guess that carried some weight as far as being selected to become chair of the RTOG.
Tacey Ann Rosolowski, PhD:
Uh-hunh (affirmative). When you were a resident, what were the studies that you were doing that helped you frame this approach?
James D. Cox, MD:
One of the studies I was doing had to do with cancer of the breast. Another one had to do with cancer of the cervix, actually very early cancer of the cervix—what’s now called—well we call it carcinoma in situ. It now goes primarily by the title intraepithelial neoplasia—what’s this?
Tacey Ann Rosolowski, PhD:
Shall I pause the recorder? Do you need to—
James D. Cox, MD:
No. Okay, I know what they need. I have to do something.
Tacey Ann Rosolowski, PhD:
Okay, I’ll just pause the recording.
James D. Cox, MD:
Yeah. [The recorder is paused.] Tacey Ann Rosolowski Ph,D Let me just get this back on. Okay, we’re recording again. So you were talking about the breast and cervical cancer that you were working on as a resident.
James D. Cox, MD:
Uh-hunh (affirmative).
Tacey Ann Rosolowski, PhD:
And what were the studies that you were running? What exactly were you doing?
James D. Cox, MD:
Well they had treated a series of patients with intraepithelial neoplasia with radiation therapy at that time which was not—this is in the very, very early days of treatment of intraepithelial cancer of the cervix. The standard treatment was hysterectomy . We were trying to spare patients a hysterectomy and give them an opportunity, actually, to still bear children. And so it was not my hypothesis, but that of my mentor, that you could do this with very localized radiations delivered only to the cervix. So I pulled all those patients together, wrote them up. It was a retrospective study. It was prospective on his part, but for me it was just gathering the data. Now interestingly, the study that we were doing on cancer of the breasts was to go back and review all of the patients that had been treated at the Penrose Cancer Hospital and have the path reviewed and try in a very primitive way at that time to understand better the findings in pathology that would predict recurrence or no recurrence. Unfortunately, that never got completed because my mentor was interested in something else, and we just never got it completed.
Tacey Ann Rosolowski, PhD:
What was the—
James D. Cox, MD:
But it was the discussions with him about that, whether it was with lymphomas or whether it was cancer of the prostate. All of those were situations where we asked that question. In about 1983, actually, I had a symposium at the Medical College of Wisconsin that was published in a NCI—it wasn’t called an NCI monograph—I think it was called Cancer Treatment Symposium. We had some funds to invite some people from around the country, and many of the people working in cancer came and addressed this issue—patterns of failure. It was published. Many people have told me over the years that it was a really remarkable body of data because we asked them to come not just with opinions; we asked them to bring data. They did, and it was a rich resource. But that was a carryover of this effort on patterns of failure.
Recommended Citation
Cox, James D. MD and Rosolowski, Tacey A. PhD, "Chapter 08: Early Clinical Studies" (2013). Interview Chapters. 790.
https://openworks.mdanderson.org/mchv_interviewchapters/790
Conditions Governing Access
Open
