Sequential Therapy for Metastatic Pancreatic Cancer - Episode 3
John Marshall, MD:We prescribe a whole lot of chemotherapy, but most of us have never taken it or taken it home with us, for example. And so, we have this idealized vision of what it’s like, and we mostly see that patient like 2 weeks later after they’ve recovered, so we’re not seeing them at their worst, typically. I think that’s a great oncologic trick. So, as best we can do, we need to describe to patients how they’re going to feel.
For me, the gemcitabine/Abraxane is really a pretty easy regimen to describe how one feels cause it’s quite predictable in terms of the acute side effects. They are very manageable, the nausea is minimal. Most people, I say, can drive themselves back and forth to get the treatment. I talk about cumulative side effects and the need for blood counts. And then I talk about the different regimens, different recipes: the 3-weeks-on/1-week-off, the every-other-week, and the 2-weeks-on/1-week-off. Because patients are setting in their calendars these regimens, and a lot of times we look up, “Okay, it’s 3 weeks on, 1 week off.” Well, if everything in that patient’s life is set for that and then on week 3 they can’t get the treatment cause their counts are too low, their whole world is now in turmoil. So, giving them a sense that this is flexible and we change on the fly, I think is really important for that regimen.
I also emphasize that we’re going to do this for a couple of months. We’re going to follow your marker, we’re going to follow you, and we’re going to then do repeat scans and see if it’s working or not. Depending on how you’re doing and how the scans are doing, we’ll make a decision about going forward beyond that.
The FOLFIRINOX is a little bit more time-consuming and challenging to describe because you have the mechanics of the treatment itself: half a day or more in the infusion chair, getting the oxaliplatin and the irinotecanthe premeds that are required—taking home an infusion pump for 46 hours, and the post medications that are really required to keep people’s nausea down. And then, the fatigue that comes, what I call the “disconnect day.” So, that second day, third day of treatment, patients, I tell them the couch looks really good, feels really good, you can get around, but you don’t really want to. Eating’s kind of off. Not so much you’re throwing up, but you just don’t want to eat for a few days. And then you start to feel better. A week later is when the diarrhea hits. Everybody’s thinking diarrhea, but you actually are constipated for the first 3 or 4 days because of the antinausea meds. Then, diarrhea a week later, if you’re going to get it, and then you worry about low blood counts, too.
It’s one of the few regimens, as a GI oncologist, in which I routinely give growth factor. In most patients, that means bringing them on day 3 to have the growth factor administered. Different doctors in different offices manage that in different ways, but we routinely add growth factor in. We, too, plan for about 4 rounds of that. So, we see them every 2 weeks, we check their labs, we adjust accordingly to how much their side effects were, we adjust the doses, and then, again, watch markers, watch patients, and watch scans. And depending on how they’re doing, set off for more treatment with that. It’s very hard to give much more than about 8 rounds of FOLFIRINOX total, and I tell that to patients up front. We have some specific goals we’re setting: we want to get the cancer back; we want to drive it back. With gemcitabine/Abraxane, it’s much more of an open-ended scenario. If this is going well, we’ll just keep it going. With FOLFIRINOX, to me, it limits setting. I’ve got about 8 cycles I can give.
We have to remember the initial clinical trials were different. So, the FOLFIRINOX clinical trial done in academic centers, PS 0 and 1, had an age cap. Not that these people were marathon runners, but they were the best of the best and they were managed in academic centers where they have disease-specific teams. The gemcitabine/nab-paclitaxel clinical trial was a community-based study. You could have a performance status all the way down to 2, and there were plenty of patients over the age of 70 in that clinical trial. I always think of that as more real-world pancreas cancer. Pancreas cancer is different in my center than in our community centers, for example. The patients who can make it to me typically have a better PS, typically are younger, etc. Whereas the patients who make it to their community doctors are a little older, have more comorbidity. So, anyway, the gemcitabine/nab-paclitaxel trial is more real world in that. And when they look at those various groups, if you pull out the high performancestatus patients from the gemcitabine/nab-paclitaxel and the FOLFIRINOX clinical trial, those 2 groups perform very similarly.
When you look at the overall clinical trial, there’s some debate about whether the gemcitabine/nab-paclitaxel is weighted differently because of the lower performance status and the higher age group. I believe that in clinic and in practice. That’s why I say I don’t think there’s a lot of difference patient-for-patient between the 2 regimens.
Transcript edited for clarity.