The two randomized trials looking at preoperative induction chemotherapy prior to surgical resection in

3A patients. A trial from Barcelona that was published in the New England Journal a few years ago but
these were both small trials. They were both designed to have 120 patients in them. They were both
stopped after 60 patients by LUNG CANCER Page 7 7 independent review boards that thought that the
results were so compelling that it was not ethical to continue the trials so that each had only 60 patients,
here 30 on each arm, this is 32 and 28. This arm is surgery alone and in Barcelona everybody got
radiation so it's surgery plus radiation versus chemotherapy plus surgery plus radiation. At the M.D.
Anderson they got surgery and chemotherapy prior to surgery. Some of these patients also got radiation
if they had close margins or residual disease in their lymph nodes. The chemotherapy was used, and
actually again the greatest chemotherapy, in Barcelona they used cyclophosphamide and cisplatin and in
M.D. Anderson they used cyclophosphamide which was pretty worthless, cyclophosphamide and
cisplatin. So these aren't the kinds of modern regimens that everybody used but still the results are kind
of interesting. The third trial at NIH that never really reached the pinnacle of significance because it only
had about 27 patients in it. It showed the same trend as these two studies. The multiple number of
phase 2 trials that were done also showed the same kind of results in a nonrandomized fashion. But if
you look at the results here in surgery alone, 85% of resectable in Barcelona, the median survival time is
only 8 months and 10 months in M.D. Anderson. These were criticized a little bit saying, "Well this is not
what we would expect because surgical time is usually longer than that". But this data has been looked
at in terms of the Lung Cancer Study Group, they included thousands of patients and it is actually
consistent with those controls for this stage of disease. If you look at chemotherapy prior to therapy, the
median survival time is at 26 months for Barcelona and actually it is up to approximately 60 months or 5
years in M.D. Anderson. So that is pretty compelling and you would think that this would be a
reasonable thing to do although people now have discounted a lot of this because some of the data that
was collected regarding K-RAS expression in these patients and both of these groups went back and
looked at the K-RAS expression and it was not balanced between the two groups. So now people just
throw out all of the results because of that which I think is a little bit unfair because that was one of the
goals of the trial was to better the K-RAS.