Dr. Raymond Russell and Dr. Kerry Russell, Cardiac
Side Effects of Chemotherapy
September 15, 2010
Welcome to Yale Cancer Center Answers with Dr. Ed Chu and Dr. Francine Foss, I am Bruce Barber. Dr. Chu is Deputy Director and Chief of Medical Oncology at Yale Cancer Center and Dr. Foss is a Professor of Medical Oncology and Dermatology specializing in the treatment of lymphomas. If you would like to join the conversation, you can contact the doctors directly. The address is canceranswers@yale.edu and the phone number is 1888-234-4YCC. This evening, I will be sitting in for Ed and Francine and my guests are Dr. Raymond and Kerry Russell. Raymond is an Associate Professor of Medicine and Diagnostic Radiology and Kerry is the Associate Professor of Medicine Cardiology at Yale School of Medicine and they are joining us this evening to talk about the side effects of chemotherapy on the heart. The Russell's are married, and I am assuming that it is probably relatively rare for a couple to share this interest.
Raymond
It is true actually. We did not get to know each other because of a
longstanding interest in chemo cardio toxicity, but I guess the
other way around. Both Kerry and I went to medical school together
and graduate school, both those were down in Houston and we came up
to New Haven to do residency and cardiology fellowships and stayed
on faculty and since then have actually developed a strong interest
in the side effects of chemotherapy on the heart.
Barber
Explain to me a little about what all of this involves.
Kerry
This is somewhat of an emerging field because of unanticipated side
effects of newly developed drugs, and I had the good fortune of
actually studying one of these drugs when I was a graduate student
at MD Anderson Cancer Center in Houston. I had a longstanding
interest in cancer biology and developing new strategies for
treating cancer, and it was a very exciting time because people
were really beginning to dissect out the molecular mechanisms by
which cancers grow and I think people were very focussed on cancer
itself and not on a lot of other organ systems that could
potentially be affected. It turned out that this drug that was
being developed, which is now called Herceptin and is very
effective in the treatment of breast cancer, also has cardio toxic
side effects. As I did additional training I ended up being
very interested in cardiology in the clinical setting and
everything was brought full circle when it turned out that this
drug actually has side effects in the heart, and now my research
labs have been studying the particular target of Herceptin in the
heart and looking at can we develop strategies to A., Protect the
heart from Herceptin cardio toxicity? Because it's a very effective
cancer drug and B., Can we also target those molecules in the heart
to treat patients with other forms of cardiac disease?
Barber
You obviously both had a background in science before you met, but
let's go all the way back to early school, when was it that science
became interesting to you?
Raymond
It's funny because we really did approach and come to it from
different pathways. I have always wanted to be a doctor and
so the clinical side of medicine was always of interest to
me. In elementary school when you were asked what you want to
be when you grow up, I wanted to be a
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doctor. So during high school and college that continued to
develop and I did not think that much about the research side of
medicine until I got to medical school and actually worked with an
absolutely fantastic cardiologist who was one of Hans Krebs' last
graduate students. Hans Krebs won a Nobel Prize for his work
in metabolism. The lab was very interested in cardiac metabolism,
and I just became fascinated with some of the aspects of that and
the translational research aspects of how you can take what you
learn at the bench side and take it to the bed side and help
patients. And then in graduate school I became very
interested in the research aspects of cardiology and in heart
research. Then when I first started my own lab I started
looking at heart failure and was drawn to the affects of one of the
other chemotherapeutic agents, doxorubicin or Adriamycin, and its
affect on heart function, which now for over 40 years has been
known to have cardiotoxic affects, and this was just heightened by
the fact that my clinical expertise is in nuclear cardiology, where
we look at heart function with a test called an ERNA or a MUGA scan
and so every day that I would read out studies, at least two
or three studies would be of patients that were undergoing
chemotherapy in which we were evaluating their heart
function. I really saw my clinical interest and my research
interest coming to a focus and that's been very exciting to now
look at the mechanisms that are responsible for that cardio
toxicity and try to identify both pathways that may be cardio
protective as well as the pathway that are responsible for that
damage.
Barber
How about you Kerry? What was the thing that got you
interested in the science aspect?
Kerry
Actually, I had a high school biology teacher who took us on a
field trip to MD Anderson. I grew up in Houston and we
visited a breast cancer imaging lab and I was so completely turned
on by the idea that you could apply science and math to learning
about human disease and so I wanted to be a scientist. I had
no concept of what a doctor did. My whole family is artists
and musicians and I would like to say, I was the talentless one, so
I did something else. Science and math were always
interesting and easy for me and when I put that together with the
idea that you could apply that in such a helpful way to patient
care, which is what caught me and made be decide to go to medical
school.
Barber
Although there really is very much an art to math and science is
there not?
Kerry
Yeah, I think that's true. That is something that you don't
get when you are kid and comes with maturity, and certainly
medicine is almost more of an art than a science.
Barber
With this background and this expertise tell me what's going on in
the lab?
Raymond
When you do research, it's really informed both by your past
experiences and hypothesis as well as work other people do, and you
take information from journals, from meetings you have been to, and
discussions in the hallways and use those to then say for example,
I wonder if this particular
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protein may play a role in protecting the heart against cardio toxicity. And your inspiration can come from the most unusual place and you may not have expected that you would put these two very desperate pieces of information together and come up with a hypothesis and then follow that out. You come up with your hypothesis and you try to figure out the best way to examine it and that might be either in isolated cells maybe using animal models and then eventually if those prove to be positive studies, then beginning to explore the questions in patients.
Barber
Kerry, you referred to this earlier, with chemotherapy you are
obviously trying to kill the cancer cells while doing as little
damage as possible to the healthy cells, and you also referred to
the fact that there are these great new drugs. What is the
process by which you identify, as Raymond has said, something that
is an area of interest and then focusing on it?
Kerry
In some cases, like for the story of Herceptin, I think that it was
purely an accident and I don't think people had any idea that this
was going to have cardiac side effects and that was purely through
observation in clinical trials that people recognized patients were
developing changes in their heart function, but I think that has
opened our eyes to being a lot more careful about the potential
cardiac side effects of newly developed drugs and that was the
impetus for developing cross talks between the oncology community
and the cardiology community so that we can be aware of potential
cardiac risk factors for these drugs and we can also learn about
the drugs that they are using which we're largely unfamiliar with
as a group and help them develop ways of protecting the heart, and
also use that information, as I eluded to earlier, to develop new
treatments that are directed at heart failure patients independent
of those receiving chemotherapy.
Barber
To what extent is it important for patients to be aware of the
things we are speaking about today and what role does the
physician, the oncologist play?
Raymond
It's very important to give a patient as much information as
possible about what their therapy is going to involve and what they
can expect from it. We do that every day when we are talking to
patients with heart conditions who don't have cancer, but I think
it is especially true when you then add on chemotherapy in which
there are risks of developing heart failure. I think the
oncologists, certainly here at Yale and at Smilow are very good
about letting patients know what to expect. Unfortunately, with
respect to heart failure, there are some fairly non specific
symptoms that people can develop that can be purely because of the
chemotherapy but not because of effects on the heart. Fatigue
and shortness of breath are two very common side effects from some
of the intensive chemotherapy regimens and those can also be seen
in heart failure and so it is very important for patients to let
their physicians know what sort of symptoms they are having, how
they are tolerating chemotherapy, and then the oncologist who is
certainly aware of those side effects and can, when necessary, talk
to the patient and to a cardiologist about further evaluation
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for those patients.
Barber
You are very busy aren't you? What I found very interesting about
this and it is great for you to spend the time because I know how
busy all of you are. How do you manage the two important ways
you can allocate your time, which would be one, the treatment of
patients and two, the research into the science?
Kerry
I will say that we wear a lot of hats. There is a lot of
juggling and the good thing about it is that each aspect has its
own rewards and its own frustrations. The research lab is a
place where you can spend that quality intensive cognitive time
reasoning through questions but it has its own frustrations and you
have to write grants and write papers and subject yourself
constantly to critique from colleagues and you can go very slowly
and you can put a lot of effort into something that never really
pays off. On the other hand, patient care is something that
always happens and there is always the reward of working with
people, which is fantastic, but that has its own frustrations as
well, dealing with insurance companies and those kinds of issues. I
enjoy going back and forth. I think most people, in order to
have success in both areas, have to choose slightly one over the
other and one of the nice things about having a focused area is
that you can stay up to date with it and be a leader in the field
as opposed to being in general cardiology.
Barber
We are speaking with Drs. Raymond Russell and Kerry Russell,
husband and wife. We are going to take a short break and we
will be back. We will talk about some of the things that are
on the horizon both in your practice of medicine and also in the
field in general.
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Barber
We are speaking with Drs. Raymond and Kerry Russell about cardiac
chemo toxicities. When we left off we were talking about a lot of
the science and what has been going on in that aspect. I want to
now look forward into something that sounds very exciting and is
something that you are working on, which is a specialty care
program. Tell me a little about that.
Kerry
This is, as I mentioned, a newly emerging field and at most cancer
centers now they are developing the need for some sub-specialty
care in this area, and with the opening of the new Smilow Cancer
Center we are very excited to start a program in this area of
specialization here at Yale. There actually are two national
meetings going on this year at other cancer centers, one at
Vanderbilt and one at MD Anderson. As a group cardiologists around
the country are establishing these programs and it is a chance for
us to all grow and learn and give much better care to patients as
far as their heart goes in the setting of chemotherapy, because
with the new chemotherapeutic agents we expect people to live much
longer lives and we want to make sure their heart stays healthy to
enjoy that.
Barber
That is an interesting thing that is happening, we solve these
problems and people are living longer, but then you do have
problems associated with that.
Raymond
Absolutely, and I think it's especially true in patients who had
childhood cancers and very fortunately they are living to ripe old
ages, and long-term effects of their chemotherapy may start
affecting their heart, or they will have had the chance to develop
garden variety coronary artery disease, and so I think the ability
to interact with the oncologist and provide specialty care for
patients who have cancer, not only to deal with the affects of
their chemotherapy, the affects on heart function, but then also to
help inpatients who have coexisting coronary artery disease and
cancer, or to help evaluate patients for specialized therapy in
which there may be increased risks to the heart muscle. This
will be very important and is an area that we are very excited
about contributing to.
Barber
Is that something you have got to tease out, whether the heart
problem was related to the chemotherapy or to something that was
preexisting?
Kerry
At this point, we do not have refined treatments specifically for a
lot of these cardio toxicities. I think there is another
really important thing that we as a national and international
community of cardiologists and oncologists need to develop which
are collaborations and multicenter trials, because right now we
treat every heart failure pretty much the same and for many of the
newer drugs we don't really have a great idea of what the mechanism
of the toxicity is or any of those kinds of things. It's a
moving target in a way and there have been only a few trials so far
looking at traditional cardio protective drugs that we used for
lots of other kinds of heart failure in patients
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undergoing chemotherapy. It's a chance for us to develop new strategies and I would say at this point we don't have fine tools for dissecting out in a patient what the cause of the cardiac complication is so we are not to that fine of a level yet, but hopefully in the future we can develop specific strategies for treating this side effect.
Barber
You mentioned the fact that there are these meetings where it's a
collaborative environment to get a bunch of people together to talk
about these issues.
Raymond
Yes, as Kerry mentioned it's a very young field, and so everybody
is going at it with a lot of enthusiasm to get together the
oncologists and cardiologists and identify what the problems are
from both sides so that we have a common vocabulary to understand
what the issues are and to identify what tests are at our disposal
to help identify what the etiology of a particular heart problem
might be in a patient who has cancer and is undergoing
chemotherapy. But then also to collaborate in a multicenter
way to learn more about these complications and help us identify
biomarkers, blood tests, or noninvasive imaging techniques, or even
genetic tests that might help us identify patients that are at risk
for some of these cardio toxicities. I think that these are some of
the things on the horizon that are very exciting in this very early
stage of the field.
Barber
You mentioned clinical trials briefly earlier, is that something
that's important for patients to express an interest in
participating in?
Kerry
Yeah, and again, with the opening of Smilow, I think we are going
to have a lot of patients that will be on trial drugs for their
cancer treatment, and I think that we need to have our eyes open
and get those patients help in trying to detect any potential
cardio toxicity for these new drugs.
Barber
In the science part, I would imagine that it becomes very exciting
to have better records and more done with digital technology and
the ability to share information and collaborate?
Raymond
Absolutely, an important aspect of research is having reliable
accurate reproducible data, and in the lab that is fairly easy to
do. When you go into the clinical setting, there are so many
more variables that enter into it and being able to accurately
track a patient to get data from a patient's chart in a reliable
and somewhat easy manner, rather than flipping through 300 pages of
handwritten charts, is a big help. And like most physicians, we
have horrible handwriting, so that can just double the amount of
time it takes, so having electronic medical records is very
important and really helps with identifying complications, of
identifying patients that we can learn a great deal from.
Barber
What is some of the research that is emerging right now that's most
exciting to you?
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Kerry
There are two ways to answer that. The first is from a
clinical standpoint, we have newer technologies to try to dissect
out cardiac dysfunction in an earlier and more sensitive way and I
think some of that is going to allow us to pick up on small changes
in cardiac function before they become severe, and those are
primarily imaging modalities like specialty cardiac ultrasound
which is one the things that I work in and other types of cardiac
imaging like cardiac CT and cardiac MRI, so the imaging field has
really taken leaps and bounds forward, and I think that's a very
exciting area. From the basic science standpoint, we have a
lot of newer types of genetic models of human disease that allow us
to hopefully pre-test some of these agents for cardio toxicity, and
people are a lot more aware of this so hopefully in preclinical
testing some of these drugs will undergo more rigorous screening
and help us to identify potential toxicities before they occur in
clinic.
Barber
Not to send everybody out to the imaging facility, but would it
help you to have baseline stuff?
Raymond
Yeah, so before someone starts chemotherapy it's a standard of care
to assess the heart's function, left ventricular function, either
through a nuclear scan that I mentioned before, a MUGA, or through
a cardiac ultrasound to identify whether or not someone has
baseline heart dysfunction, and if that's the case, that
would be the sort of person we would see even before they start
chemotherapy to help make decisions of how they can optimize their
treatment, but at the very least to establish what their baseline
function is. In addition, if patients have any sort of
concern about coronary artery disease either because of the
presence of chest pain or multiple risk factors for coronary
disease, that sort of patient may benefit from having a stress test
to help identify what we call their risk of having a heart attack
in the future, and that can allow us to initiate therapy once again
to help protect the heart in the setting of continuing
chemotherapy.
Barber
Let's talk a little about once you realize there is chemo toxicity,
what's the process? How do you treat that?
Kerry
Because, as I said, we don't have very fine tools at this point,
there is big discussion that needs to go on between the patient,
oncologist, and cardiologist about what the relative benefits
are. In many cases, we have good therapies for treating mild
heart failure and in many cases we can deal with the heart problem
in favor of treating in cancer if the cancer is responding to the
chemotherapeutic drug. In some cases we will have to
collaborate with the oncologist to change the chemotherapy to
something that's less cardio toxic. So far, in my experience, many
times we can make it through in favor of being able to use these
very potent drugs to treat the cancer. So it's really an
important collaboration. As you pointed out earlier, we are trying
to kill the cancer without killing the rest of the patient, and I
think that an informed discussion about the relative risk and
benefits of the therapies with the knowledge that often we can
treat mild heart failure very
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effectively to get the patient through and be able to be cured from their cancer, those kinds of discussions are very important.
Barber
Are there preventive measures to take when you are aware of these
risks?
Raymond
There are, one is actually fairly straight forward, not necessarily
always simple, but fairly straight forward, and that is to have a
healthy lifestyle in the setting of your ongoing therapy.
There have been studies that have demonstrated a cardio protective
effect against the chemotherapeutic agents by exercise, and so
that's something that is obviously good for everybody anyway, but
can certainly help protect against some of the effects of these
chemotherapeutic agents. In addition, there have been small
studies that demonstrate certain medications that may help protect
the heart, and these should be considered I think in patients that
are certainly at higher risk for developing cardio toxicity, but
the studies tend to be fairly small and they have not been
overwhelmingly conclusive to the point where we would say
absolutely everybody on this particular chemotherapeutic agent
should get this drug to help protect their heart.
Barber
It sounds like we are getting somewhere with this and that this
field has just started to develop and it must be really a very
exciting time for both of you.
Kerry
Yeah.
Raymond
It absolutely is. It is great to have the intellectual
collaboration with the oncologists and obviously, taking care of
patients is why we got into medicine, and so helping a patient deal
with what can be a very devastating disease is quite rewarding.
Barber
My thanks to Drs. Raymond and Kerry Russell for being with us this
week on Yale Cancer Center Answers.
If you have questions or would like to share your comments, visit yalecancecenter.org where you can also subscribe to our pod cast and find written transcription of past programs. I am Bruce Barber and you are listening to the WNPR Health Forum on the Connecticut Public Broadcasting Network.