DR LOVE: Ed, if this patient came to see
you today postoperatively, what would you
be likely to offer him?
DR KIM: If he were in very good shape,
I probably would consider a carboplatin-based
regimen, although the polycystic
kidney disease does bother me. I prefer to
use docetaxel rather than paclitaxel. It has
fewer side effects, especially neuropathy.
DR LOVE: Mike, how did you treat
this patient?
DR TRONER: He was treated with carboplatin
and paclitaxel therapy and tolerated it
reasonably well, although he did have some
moderate toxicity. Dr Kim, I am intrigued
by your comment about docetaxel being
better tolerated than paclitaxel. My clinical
impression from our patient population
is that we tend to see more skin toxicity,
peripheral edema and, most significantly,
asthenia with docetaxel.
DR KIM: May I ask what dose of paclitaxel
you’re using?
DR TRONER: It’s low. On an every
three-week schedule, it is probably 135 to
150 mg/m2.
DR KIM: That’s the real issue. We tend
to underdose paclitaxel a bit. If you used a
similar dosing schedule with docetaxel, you
would be dosing anywhere between 45 and
50 mg/m2 every three weeks. So if you’re
using 75 mg/m2 of docetaxel and you’re
not using 225 mg/m2 of paclitaxel, I would
totally agree with your statement that you
would see better tolerability with paclitaxel.
But I would challenge you that if you used
45 or 50 mg/m2 of docetaxel, you would
find it to be very well tolerated, with less
asthenia as well.
DR LOVE: What happened with further
follow-up?
DR TRONER: He did okay for a couple of
months. I was about to restage him when
he came into the office with increasing fatigability,
some chest discomfort, dysphagia
and esophageal pressure. Once again, he
had an unremarkable physical exam, but a
repeat PET/CT scan showed moderately
extensive mediastinal disease with both
paratracheal and subcarinal lymphadenopathy.
DR LOVE: Roy, what are your thoughts?
DR HERBST: This is a difficult situation,
with a symptomatic patient who is
primarily refractory to platinum-based
therapy. My next step would be to consult
a radiation oncologist right away. Then the
decision is whether to treat him with radiation
therapy alone or try to bring in some
second-line chemotherapy in combination
with radiation.
Not many good alternatives exist right
now. We have some data on pemetrexed in
combination with radiation (Seiwert 2005).
It is pretty well tolerated, so one option
might be to administer that in combination
with carboplatin.
I’ve done that on a few occasions for
patients like this. I still probably would use
some carboplatin, too, and you can administer
that with the radiation therapy. Radiation
therapy would be the way to go here.
DR KIM: Assuming the MRI of the brain
is negative, then we’re looking at a local
recurrence of his primary disease growing
through chemotherapy, which is obviously
of concern, but it’s still local disease. I agree
with Roy that radiation therapy is the first
option we would consider.
If we wanted to treat with the best intention
and take a risk, we could use a concurrent
chemoradiation schedule because it
is just local recurrence. That would be a
multidisciplinary discussion between the
surgeon, the radiation oncologist and the
medical oncologist.
If we wanted to use chemotherapy with
radiation therapy, then certainly docetaxel
as a single agent is a possibility. The other
regimen that I use often is cisplatin with
docetaxel, both weekly. Hak Choy has
conducted studies using carboplatin with
docetaxel and radiation therapy
(Choy 2001).
DR LOVE: Do you see bevacizumab
fitting into this man’s therapy, either now
or in the future?
DR KIM: If we considered his disease
metastatic and we used the radiation
therapy as a local control measure
because of his symptoms, then I
wouldn’t have a problem giving him
bevacizumab afterward.
DR LOVE: Roy, what about the
general concept of second- or third-line
bevacizumab?
DR HERBST: I believe that, in most cases,
bevacizumab should be used in the front-line
setting. But in a case like this, one
could consider a chemotherapy combination
with bevacizumab once the radiation
treatment is complete.
Trials combining bevacizumab with radiation
therapy have developed slowly because
of concerns about central lesions and about
tumors of this type bleeding. The RTOG
and SWOG both will soon have trials
evaluating bevacizumab with and without
radiation therapy.
Right now we do not have data, so I
probably wouldn’t add it to the radiation
therapy, although every preclinical paper
you read shows anti-angiogenic agents
improving short-term oxygenation to the
tumors, enhancing the radiation effect
(Gerber 2005). In my opinion, that is going
to be a real winner, but it’s going to take
some time.
I do think this patient is a great candidate
for a second-line protocol that includes
docetaxel with bevacizumab, pemetrexed
with bevacizumab or erlotinib with bevacizumab.
These trials are all out there.
DR LOVE: Mike, can you follow up with
this patient?
DR TRONER: He will be seeing the radiation
oncologist next week. My treatment
plan was weekly docetaxel, but I am also
considering bevacizumab.
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