Chemotherapy Late Toxicities - Dr. David Margileth

Uploaded by drjayharness on 22.12.2011

>>> DR. DAVID MARGILETH: Late toxicities of chemotherapy are a major issue and we obviously
want to maximize the cure rate but minimize late toxicity. In some situations that’s
not possible, in other words in some cancers, we need to use drugs that we know may introduce
a late toxicity, to maximize the cure rate. Nobody would elect not to be cured because
of a 3 or 4% risk of leukemia, for instance in Hodgkin’s disease treatments, eight or
ten years after the treatment.
In breast cancer, one of the thrust of research in the last ten years has been ‘How can
we modify treatments such that we minimize late toxicity?’ Adriamycin is, or was, a
very commonly used drug in breast cancer and in the last five or ten years, it’s become
apparent that at least in many instances that we commonly used Adriamycin, we don’t need
to use that drug anymore.
That’s especially true in the case of tumors that over-express this growth regulatory gene
called the HER2 new gene, which is over-expressed in about 20-25% of breast cancers.
Herceptin is a drug that has greatly improved those patients’ prognosis but it has some
mild late heart effects, and when it was combined with Adriamycin, the cardio toxicity became
a much more important issue.
When the trials were reported in 2005, of what are called non-Adriamycin HER2 based
chemotherapies, that incidents of cardiac problems, namely congestive heart failure,
went way down. So we now have eliminated a lot of potential heart problems in patients
with more aggressive breast cancers.
In addition, in patients with better prognostic breast cancers that still need chemotherapy,
we have replaced an Adriamycin and Cytoxan regimen with a regimen of drugs called Taxotere
and Cytoxan, wherein that combination has no late term heart problems whereas the Adriamycin
had 4-5% incidents of cardiomyopathy or congestive heart failure.
So one of the goals has been to minimize heart problems. One of the other major issues we
deal with obviously in much younger women is the whole fertility issue, and there are
number of trials looking at different combinations of drugs, or additive drugs, that might be
able to preserve fertility in a situation in which we still need to give chemotherapy.
The other side effect that often comes up is what’s called chemo brain or the sense
that women’s brain sort of don’t work like they used to, sometimes after chemotherapy.
It’s been a very interesting area of research and the results have been somewhat murky.
With the general kinds of chemotherapy that we give for breast cancer, there’s not a
lot of hard scientific data that would indicate that we have done something bad to the brain.
I have a lot of patients that complain about minor issues, some forgetfulness – things
like that, but I must say I have not had people that, for instance, used to be a CPA and feel
like their IQ was dropped 20 points and have to do something else. So it’s a nuisance
issue I think for breast cancer. For patients with bone marrow transplant, however, the
leukemia-lymphoma group, there actually is some data that very high dose chemotherapy
may do something to the brain that we can describe as chemo brain. But in the breast
cancer population, at least at this point, it doesn’t seem to be a huge clinical issue.
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