Chapter 26: Chemoprevention and the Celebrex Study: Some Background
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Description
Dr. Levin sketches the work on which his studies of Celebrex and colorectal cancer were based. This study was based on the idea that pharmaceutical agents, when taken regularly, might influence the formation of lesions in the colon. Work by Dr. Gideon Steinbock (at MD Anderson) had provided early evidence that Celebrex could influence inherited cancers, leading to the study of the drug’s influence on un-inherited carcinomas. Dr. Levin lists the studies and participants. He then notes that the discovery that Celebrex caused heart problems put a damper on research into chemo prevention in colon cancer and all cancers, shifting the emphasis to safety above all else when dealing with healthy patients. He notes that in the early 90s, the discussion focused on how to approach preventative measures, concluding that risks to a healthy patient must be very low in order to undertake chemo-preventative measures. He briefly discusses a peer review group from Pfizer and the NCI which added to the sense of caution about chemo-prevention.
Identifier
LevinB_04_20130708_C26
Publication Date
7-8-2013
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Researcher The Researcher Overview Definitions, Explanations, Translations Evolution of Career Professional Practice Discovery and Success The Professional at Work Collaborations Understanding Cancer, the History of Science, Cancer Research The History of Health Care, Patient Care On Pharmaceutical Companies and Industry
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:
Okay, so let me just say it is ten minutes after ten. Today is July 8, 2013. I am interviewing, via telephone, Dr. Bernard Levin for our—actually I think it’s our sixth session together. So thank you, Dr. Levin, for joining me via telephone. I appreciate your willingness to do this.
Bernard Levin, MD:
Thank you. Good morning. I am delighted to be part of this.
Tacey Ann Rosolowski, PhD:
And you were—we had just finished up in our last session talking about the Celebrex studies and the surprise that Celebrex actually created some cardiac threats for patients. And you said that would kind of lead naturally to a more philosophical statement, so I wondered if you wanted to proceed with that?
Bernard Levin, MD:
The whole idea behind the Celebrex study and similar studies was that the use of a pharmacological agent taken regularly—daily or twice a week or three times a week—would influence the development of premalignant lesions in the colon, particularly chronic adenomas. And the early evidence showed it had an effect in people with an inherited predisposition to develop cancer of the colon, mainly in familiar adenomatous polyposis. This work was being done at MD Anderson by Gideon Steinbach as the lead author and Patrick Lynch and others including myself and colleagues at St Mark's Hospital in London leading to a publication in the New England Journal of Medicine. This was the impetus to try this drug in people with non-inherited adenomatous polyposis, so called sporadic adenomatous polyposis. And then two major trials were launched, one by Nadir Arber in Israel with me as a co-principle investigator and the other by Monica Bertagnolli in Boston with Ernie Hawk who was then at the National Cancer Institute as the two principle investigators. These were multinational studies involving thousands of patients. So although the drug was shown to have some effectiveness in reducing the number of adenomatous polyps in the colons of people affected, the subsequent discovery that there was indeed an increased risk of heart disease common to all NSAIDs put a damper on our enthusiasm for this drug. And it led to a considerable discussion about the real role of chemo prevention not only in colon—pre-malignancies of the colon, but potentially in other conditions, mainly the need to emphasize safety above all else when looking at people who are asymptomatic and extensively healthy. So the risk to benefit ratio of all interventions has to be considered, but particularly when one is dealing with a preventive strategy. For someone who is healthy, the risks have to be very low and the benefits pretty high.
Tacey Ann Rosolowski, PhD:
How did you see that—now when were those discussions taking place in terms of timeline?
Bernard Levin, MD:
They occurred in the early nineties because the review group—the advisory group was independent of each study that reviewed the data from which the investigators were blinded. But the review groups that peer reviewed were appointed by the National Cancer Institute and also by Pfizer. They were part—they were privy to the data, and they were monitoring the data. And as soon as the signal of increased cardiac morbidity or disease became apparent the study—the studies were essentially put on hold completely. And that was in the very early nineties.
Tacey Ann Rosolowski, PhD:
Now did that put a damper on future research and chemo prevention, or were there some agents that did actually kind of get through that gate?
Bernard Levin, MD:
No, it just added a tremendous sense of caution that investigators had to follow. A number of other agents were tried subsequently and safety. And the uses of low-dose drugs in combination became the attempt to mitigate side effects while maintain benefits. And there have been some—without going into great detail, there have been attempts at doing that. On the other hand, there were other studies that were tried in other conditions. For example, intervention with vitamin A or its derivatives were shown not be beneficial in people with a prior history of—excuse me, in previous smokers who had an increased risk of lung cancer developing after the ingestion of long-term vitamin A derivatives, so called beta-carotene. So we’re still evident in people’s minds for the potential for risk associated with chemo prevention and trying to reduce the development of cancer. But unfortunately, we’re finding that either the agents were not beneficial or even harmful.
Tacey Ann Rosolowski, PhD:
Where does it make sense to go next from here, Dr. Levin?
Recommended Citation
Levin, Bernard MD and Rosolowski, Tacey A. PhD, "Chapter 26: Chemoprevention and the Celebrex Study: Some Background" (2013). Interview Chapters. 1362.
https://openworks.mdanderson.org/mchv_interviewchapters/1362
Conditions Governing Access
Open
