Question: 1st question is we know that you’ve dedicated yourself in
treatment of renal cancer and testicular cancer for over 20 years,
so can you briefly talk about the latest development in treating
Kidney cancer has been considered to be a very resistant cancer to
treatment for many years. It’s actually considered a model for a
cancer that’s resistant to chemotherapy. It’s been a very difficult
cancer to treat, because it is often diagnosed at a late stage.
There aren’t early warning signs for kidney cancer. So about 1 out
of 2 of the times that someone’s been diagnosed with the cancer
they have spread to other areas.
Until recently, there have been very few treatment options to treat
people with kidney cancer in that setting so that it has been
considered to be a cancer with a poor outlook. The only 2
treatments that have yield to any benefit until recently are
cytokines or immunotherapy with 2 commonly used cytokines been
IFN-α or Interleukin-2. They only resulted in response in 1 out of
10 patients and the average survival for people with metastatic
cancer was about 12 months. Both of those medicines were discovered
in the mid 1980’s, and it’s been the main state of treatment with
no progress at all until just recently with the discovery of the
We’re basically in the era now of targeted therapies for cancer
where it is recognized that most cancers arise from some sort of
genetic mutation cancer. And so the targeted therapies have been
available largely as a result of a better understanding of tumor
biology, plus the development of molecules or medicines largely
through industry. It was recognized about 10 years ago that there
is a gene mutated that causes most cases of kidney cancer called
the Von Hippel-Lindau gene. Also in parallel different targeted
medicines were developed in laboratory and it was recognized that
they matched very well with kidney cancer. So the 2 medications
that were developed earliest and proven to be beneficial to
patients are sorafenib which is made by Bayer and sunitinib which
is made by Pfizer. They are both pills that people take that can
treat kidney cancer.
There’s other etcetera coming. There’s another drug called
temsirolimus which is made by Wyeth, is also a targeted therapy
that’s proven beneficial. Avastin (Bevacizumab) was studied in a
large phase III trial and that proved to be beneficial as well.
Most recently, another orally administrative medicine called
everolimus, which is made by a company called Novartis, is proving
effective for kidney cancer patients.
From the stand point of medical studies, these targeted therapy
medicines have replaced the cytokines with interferon; they have
been swept away and patients are treated with the targeted
therapies. They rarely result in a complete remission of a cancer.
For the most part, the medicines are used to control or contain the
cancer as long as possible. When the cancer breaks through, we will
try a different medicine. So they are all important steps in terms
of the cancer care for people with kidney cancer. But when you add
them all together, they are resulting in a much better outcome and
a much longer survival for people with metastatic kidney
Question: you mean combined?
No, they are not given combined but given in sequence.
The paradigm in the United States and Europe is in most patients to
go with the sunitinib first, because that’s felt to be the most
effective. Then if the person progresses after the sunitinib, until
recently we have always given the sorafenib as the second line.
With the temsirolimus available, temsirolimus or sorafenib is given
and then the third. So there is the first line, second line and
third line. We’re trying to sort out with clinical trials which are
kind of the best sequence to give out the medicines.
Question: So just now you mention that you use the sunitinib as the
That’s the first-line in the United States
Question: And others are the second-line？
The second and third line is sorafenib or temsirolimus. As far as
which one is the best order, it’s being addressed in a large phase
3 international trial where the patients are randomized to
temsirolimus or sorafenib as the second line. So we don’t know
which one is the better line, but for the most part, our patients
wind up getting all three.
Question: And I know that sunitinib has been used to treat advanced
kidney cancer. And I want to know how about its future for other
My focus is on renal cell carcinoma, so my understanding is that
sunitnib is being studied in a broad spectrum of other solid tumors
as well, including lung cancer, breast cancer and others. In those
cancers, it’s often given in combination in chemotherapy. It’s also
proven to be effective and approved by many regulatory authorities
for GIST as well.
Question: we all know that you have been in charge of many
international multi-center trials. Some of the trials have been
recommended by NCCN as the evidence. Can you describe the most
recently progress in the clinical trials?
In a renal cell carcinoma, the large pivotal phase 3 trials that
establish sunitinib are the first line treatment for patients with
metastatic cancer which was a randomized comparison of sunitinib to
IFN-. It was targeted to a relatively general population of
patients. We have a system that we kind of use to estimate the
prognosis (the Motzer System). It’s a 3-period system that
differentiates patients as favorable, intermediate and poor. In
that trial, the majority of people have a favourable of
intermediate. And a study showed that the progression free survival
which was the primary endpoint was longer for sunitinib compared to
IFN, and the survival was also longer as well. The overall survival
endpoint was more difficult to assess because many of the patients
on interferon arm had access to the new targeted therapies which
lengthened their survival. But that’s the main study that defined
sunitinib as the first line treatment in U.S and Europe. However,
some new data released in this year’s ASCO do show that sunitinib
can prolong patients overall survival to over 2 years to 26.4
months, which is the first time achievement in mRCC treating
There was also another study that was done of Bevacizumab or
Avastin plus interferon compared to interferon that was also a
positive study and has resulted of approval of that combination in
many countries of Europe. But it has not approved in the United
States. So that’s considered to be a second option.
Temsirolimus which has a unique mechanism of action which is called
an mTOR hyperactive specifically tailored to very poorly prognosis
patients. It was studies in a head to head comparison to interferon
and patients in that small minority of people of very poor outcome.
It showed increase survival in that group. So the nomogram in the
United Stats and Europe as well is for the first line treatment,
for the favorable and intermediate, sunitinib is the main option.
And a second option is Bevacizumab plus interferon. In the poorest
population, the largest group of evidence is for temsirolimus based
on the phase 3 trial, but sunitinib is an option as well.
For the most part, sorafenib was studied in a second line setting
compared to placebo in patients who have had old treatments. Its
use hasn’t been as successful in first line when it was compared to
interferon in first line and a smaller trial but it wasn’t better
than interferon. So mostly in our country, sorafenib is used in
selected instances in patients who maybe would not tolerate the
others but it’s more used in second and third line in our
Question: what do you think about the most significant difference
between eastern and western countries in these trials using
sunitinib or sorafenib?
I think since these agents are used globally and patients in
different countries can tolerate medicines differently. It’s very
important that there be extensive clinical trial experience in a
while spectrum of countries around the world. I think that is very
important. My understanding is that as some of these studies had
been represented from people from all different countries. If there
are gaps for areas with less experience, it will be important for
the companies to do trials specifically in that country so that the
doctors can get experiences with their own patient population. So
that’s why I think it’s very important that you do study in China
with sunitinib or temsirolimus specifically in your patient
population with your experts.
Question: what’s you opinion on the cost-effectiveness of these
I think that the striking fact with these drugs would be improved
efficacy and outlook for the patients with this disease. That
really has to be the emphasis. The fact is that patients with this
disease really had little or no options 5 years ago. And it’s a
lethal tumor with a rather quick death. So now there are multiple
medications that improve the outlook and be proved the prognosis to
lengthen survival. So I think that the countries and their
sponsoring companies have to come up with ways so that they can
offer them to their own patients with this disease. It’s
Question: I have another question, I want to find the Motzer
scoring system, but I could not find any material on that. Can you
give me some suggestions for finding that?
Years back when we were treating patients with mostly chemotherapy
or cytokines, what we did was investigating a way to see if we
could predict the outcome for people with metastatic cancer. The
reason we did this is that we could counsel all the patients and
also it would help clinical trial designed an interpretation when
medicines did become available that looked like they were useful.
So it was an underrepresented area that really wasn’t any system
for people with metastatic renal cell cancer. The point of fact is
that the medications were so poor and the course was so dismal and
there were very few doctors that focused at renal cell cancer
before. So we’ve had an extensive record for over 20 years of
trying all different medications for this disease at Memorial
Sloan-kettering Cancer Center. That’s what we do. And it was
initiated by another doctor that was there before me who’s a very
well known gastrointestinal stromal tumors oncologist. But when he
left, I picked up the kidney cancer and done it ever since, so I
establish a large database of close to 700 people that have been
treated on our trial, and we setted up that rich system. It’s
called the Memorial Sloan-Kettering (MSKCC) Risk System. It was
initially published in the Journal of Clinical Ocology in 1996
which was the primary model. There have been 2 other publications
where we kind of refined it, one to the first line and the other is
to the second line. But the primary model was in 1996 in the
Journal of Clinical Oncology.
記者: 舒尼替尼已經被用於治療晚期腎癌， 那麼您對它在其他腫瘤領域的治療前景作何理解？