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Grana, MD
Edited comments by Dr Grana
Clinical impact of CALGB-9741: Dose-dense versus
conventional scheduling
The data from CALGB-9741 was the first instance in a long time
that we saw an impact of altering dose and dose density. We’ve
been so disillusioned by the high-dose therapy concept that this
was refreshing. The data looked very promising. The disease-free
survival data was impressive. The overall survival data was less
impressive. I think oncologists are uncertain of how they will
translate the data into practice.
When this type of data is presented, it’s our responsibility
to discuss it with patients and consider what the patients themselves
have to say about it. Some patients are very educated and do a
lot of research in preparation for their treatment selection and
participate in decision-making.
I’d be very comfortable using the dose-dense regimen. We
enrolled patients in that trial. I will present this data much
as I present the data on AC/paclitaxel from the two studies that
have been done. I will then offer it as an option, but I have some
caveats and I’ll share those caveats with the patient. Patients
have to understand that I don’t believe this data has the
maturity I’d like to see.
Most of us are creatures of habit and we’ve become very
accustomed to the every-three-week regimen — the AC x 4/taxane.
I’m also somewhat concerned about the increased toxicity,
although the study did not show an enormous increase. Most of us
have an inherent fear that as we’re changing doses we’ll
have enhanced hematologic toxicity. Introduction of a G-CSF is
not going to be an issue, except that many of us are now in the
habit of using pegfilgrastim, which is used on an every-three-week
schedule. The question is: Can it safely be used at two-week intervals?
Management of patients with ER-negative, node-positive
breast cancer
Currently, I’m using AC x 4 followed by docetaxel x 4.
Both the sequential and concurrent dose-dense regimens are also
reasonable options. I find that the sequential regimen is easier
in terms of logistical planning, and that’s probably what
I would recommend to the patient. I also discuss data regarding
AC/paclitaxel, TAC/FAC and participating in ongoing trials.
Neoadjuvant clinical trial of capecitabine/docetaxel
I’m very enthusiastic about the neoadjuvant capecitabine/docetaxel
trial. The neoadjuvant approach is exciting in that it allows you
to see the effects of your therapy and what you can achieve in
terms of pathologic complete response. We need to improve on what’s
been accomplished previously. AC/docetaxel has only achieved a
25 percent pathologic complete response. Clearly, there’s
a lot of room for improvement. The addition of capecitabine in
that setting is a wonderful approach, and I’m looking forward
to the initiation of the NSABP trial to help answer that question.
CALGB-49907: Phase III trial of chemotherapy
in the elderly
I am participating in Hyman Muss’ study, CALGB-49907, evaluating
capecitabine versus AC or CMF in elderly patients. The concept
of altering chemotherapy for the elderly is very important and
timely. It’s time that we look at patients and other factors
in their lives, rather than treat everybody in the same mode. The
data evaluating capecitabine versus CMF in metastatic disease showed
equal effectiveness, so it is a timely study to be doing.
Single-agent capecitabine will not necessarily be easier to tolerate
than CMF, but it avoids some of the issues with the intravenous
use of drugs and the frequency of visits to the office. Some of
the other toxicities associated with capecitabine may make it a
little bit harder than CMF.
Capecitabine/docetaxel in the management of
patients with metastatic disease
I use the capecitabine/docetaxel regimen for a select group of
women with metastatic disease — those with more extensive
disease and with a better performance status. The regimen produces
good results but may have significant toxicity, especially at the
doses that were initially presented. I tend to start at 1250 mg/m2
twice a day for 14 days followed by seven days off as the regular
approach. If you select your patient population appropriately,
it’s tolerable. The hand-foot syndrome is manageable with
appropriate dose reductions when it occurs. The hardest symptom
complex that I encounter with that regimen is the GI toxicity.
It’s more difficult to manage and less amenable to improvement
with dose reductions.
Use of single-agent capecitabine in the metastatic
setting
I’ve had good results using capecitabine monotherapy. Like
vinorelbine, I use it in patients who do not have life-threatening
disease and are better candidates for single-agent therapy. I tend
to use capecitabine preferentially, because the single-agent data
with vinorelbine has not been particularly impressive.
Translation of the 47-month update of the ATAC
trial data to clinical practice
I was very excited to see the initial presentation of the ATAC
trial data, because the results were very believable. I went home
and began discussing it with my patients. These women needed to
be informed about the data, because they were going to hear about
it in the media. I also wanted to reassure them that, if they were
on tamoxifen, they should continue on tamoxifen.
In newly diagnosed patients, I had in-depth discussions. We talked
about the limitations and the strengths of the trial, and the majority
of patients with whom I discussed it as a viable option felt very
comfortable using anastrozole. I have used anastrozole in a large
number of patients. Now, we have 47 months of follow-up and the
early data holds. If anything, the data looks more promising, so
it gives us even more confidence in the selection of this agent.
Use of bisphosphonates in patients on aromatase
inhibitors
The data presented by Dr Gnant in San Antonio, demonstrating
that zoledronate reversed the bone loss associated with hormonal
therapy in premenopausal patients treated with an LHRH agonist
and anastrozole, was very interesting. Bone is my major concern
when I’m considering anastrozole in the adjuvant setting,
because many of these women have small cancers and, in reality,
have an excellent prognosis.
Osteoporosis and osteoporotic risks are a significant factor
for many of these women in the long term. They are not going to
receive hormone replacement therapy, so that is a factor. I have
changed my practice over the last year in how I approach bone disease.
In the past, I felt very comfortable with tamoxifen. I monitored
bone mineral densities, but I was comfortable with maintaining
women with osteopenia on tamoxifen in addition to recommending
more exercise and calcium supplements.
Now, I obtain bone mineral density at the initiation of an aromatase
inhibitor. If patients have good bone mineral density, I urge exercise
and calcium. If they have osteopenia, I initiate bisphosphonates.
If they have osteoporosis, I think long and hard about whether
that patient might be better served with tamoxifen.
We fear bone loss today, but if the bisphosphonate studies demonstrate
that they will decrease metastatic risk, then the reality is that
bisphosphonates will become commonplace in the treatment of early
stage breast cancer.
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