Resected Pancreatic Cancer: Why Wait for the Inevitable?

John L. Marshall, MD


April 04, 2014

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Hello, everybody. This is John Marshall for Medscape.

There is a lot going on in the area that we call "maintenance therapy." We are showing that, with solid tumors in particular, if you keep some treatment going, then patients actually have a delayed progression-free survival. It's translating into some improved overall survival, and this makes sense to me -- keeping some pressure on. It is counter to those who say that keeping chemotherapy going breeds resistance. I'm not sure that is right. This pressure, keeping it from regrowing, is a good idea if you can find the right drug.

In gastrointestinal cancers, one of the best drugs that we have for this may be 5-fluorouracil (5-FU) -- an oldie but a goodie, now in the form of capecitabine -- which can be given for extended periods of time. The best study that we have so far with the concept of maintenance therapy is known as CAIRO3,[1] which was presented last year at the American Society of Clinical Oncology meeting. It was started as frontline therapy, and then patients were randomly assigned to no further treatment or to continuing capecitabine and bevacizumab. The group of patients who received capecitabine and bevacizumab had a progression-free survival of about 8 months, whereas the control group had a progression-free survival of only 4 months. This was good, solid evidence that this is the way to go forward.

How does this play out in other settings? One place that we have been testing this in the so-called "adjuvant setting" is in pancreas cancer. I call these people "the inevitable." Even though they have had Whipple's and they have had adjuvant chemotherapy, and maybe radiation therapy, their odds of relapsing is almost inevitable. What do we do? We sit around and wait for them to relapse. Some of my colleagues are critical of this approach, but I couldn't stand waiting around for nodules to show up.

So, what we have been trying out over the past several years is a concept of maintenance chemotherapy in this group. We know that gemcitabine has a survival advantage and we know that 5-FU does as well, so why not combine them? We have been giving gemcitabine in the adjuvant setting, and then, either with the chemotherapy/radiation or even by itself, putting patients on prolonged exposure to capecitabine. We are pleased that our experience was just published by one of our junior colleagues here named Ben Weinberg,[2] who did such a nice job of taking our data and putting it together. It [will be] published in Gastrointestinal Cancer Research, and it demonstrated a very high level of patients who remained disease-free and are well into multiple years after having a Whipple procedure. This was a single-arm, retrospective analysis, so clearly we need a prospective analysis. It's time to do this.

We need our cooperative groups to jump on this right away, to look at different compounds in the maintenance window, in patients with locally advanced pancreas cancer after initial therapy, and particularly in "the inevitable"-- the patients with post-pancreatic resection for pancreas cancer. We could demonstrate efficacy in this setting and we would then have applicability in gastric cancer and also in the "nearly inevitable"-- the high-risk patient with colon, liver, or lung metastases that have been removed; there is a very high incident rate of events in this group. We don't cure many of them. How do we take this maintenance concept and apply it to this very high-risk group? It is our charge over the next year or two to design and implement studies for our patients in with bad cancers.

Immunotherapy, 5-FU, and other targeted agents as maintenance are very important. We will see it happening. It's our job to deliver these kinds of clinical trials. If you have those trials around, put your patients on them. This is a very important question that I believe will have a major impact on the outcome of our patients with gastrointestinal cancer. This is John Marshall for Medscape, talking about maintenance therapy.


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