Choosing Chemotherapy for Pancreatic Cancer

John Marshall, MD:We’ve got choices now for managing frontline metastatic pancreas cancer, and so it really falls on us to work with our patients to understand what the best, say, frontline therapy is. And when I approach this, I think about a 3-drug cocktail (the FOLFIRINOX regimen) or a 2-drug cocktail (the nab-paclitaxel/gemcitabine regimen). We have to remember that they’re not very different in how well they work, but they are very different in how well they’re tolerated. And so, there tends to be this drive to say, “Well, in a very good performance status patient with a lot of support, I’m going to go with the 3-drug regimen first because I can.” We tend to favor that. But I do really think we have to have a good discussion with our patients. What is their level of support? How will they do with an infusion Mediport pump at home? Neuropathy, the oxaliplatin neuropathy, is it immediate and significant? The nab-paclitaxel neuropathy is later and cumulative and fades. So, you want to make that decision.

I think it’s even harder in a case like this, where it’s localized disease, where you think you might maybe just convert a patient to resectability. Now, we have to remember, in our case, they found liver metastases, so we’re probably not going to go to surgery. But there are a lot of times of locally advanced pancreas cancers where we still cross our fingers, and if we get a good enough response, we might take them to surgery. And here, we tend to want to go to 3-drug cocktails. But quite honestly, the 2-drug cocktail performs very nicely in that setting, too. So, it’s working with your patient, understanding what their support is, what they’re willing to put up with, and making your best clinical judgment.

So, when a brand new pancreas cancer patient comes to see us in the clinic and has metastatic disease—and we’re trying to really set expectations, what are our goals, how are we going to go forward, what are our expectations of treatment—I really do start with some language around the severity of the disease, that this is a serious cancer, that it is life-threatening. Most of them honestly have done a little clicking already so they know something about what they’re facing. But I just want to level set with them where we are.

We want to manage their symptoms, tell them we’re going to take care of them forever, and make sure they’re doing the best they can. And then, we turn to the positive side of this, and that is, we’ve got new treatments. Those treatments, by themselves, are not curative. I often will use language of, “The only way we know to cure this disease is through surgery,” and then say, “But you’ve got too many spots for surgery.” So, I don’t actually say, “You can’t be cured,” but I let them figure it out on their own. Maybe I’m just a chicken and should just come right out and say it. But they understand what I mean by that.

And then, with that, we talk about survival, we talk about the positives and the impact of treatment. I usually dive right in to discussing the regimens that are used: that the 2 main regimens are the 3-drug regimen (FOLFIRINOX) and the 2-drug regimen (nab-paclitaxel/gemcitabine). And I usually start with the 3-drug regimen. I describe what a Mediport is, how one is put in, why it’s a nice thing to have. I then describe the regimen in some detail—how much time, how often they come, what the side effects are—and this takes some time, and I really feel that it’s important for us to take this time. Different practices do this differently. Sometimes doctor practices will have their nurse practitioner or their nursing core do the describing of that. But I actually think it’s really important for the doctor to sit down with a patient and try and describe what it’s going to be like, how they’re going to feel—not just the 2 days on the treatment, but a week later—and how many good days, how many bad. Because that patient is having to make some decisions about their life. If they’re working, for example, can they continue to work? Are they going to need a ride back-and-forth from treatment? And they’re doing all of that math while we’re describing this neuropathy and that nausea, etc.

We also have to remember that almost everything we tell a patient, particularly on that first visit, they forget or they didn’t hear. And so, if there’s not somebody sitting right next to them writing everything down or they’re recording you on their iPhone, then make sure that they get written information, tell them you’re going to discuss it again with them, in detail, because they will have forgotten a lot of the detail that you think they’ve gotten.

So, first I describe the 3-drug regimen in some detail. And then I say, “Or behind curtain number 2, we have a 2-drug cocktail.” And then I actually go into not only the specifics of the 2-drug regimen, but how they’re different. Why would anybody pick 3 versus 2? And why do we think that there’s a little bit of superiority to the 3-drug regimen than to the 2? I describe actually the clinical trials, how one was done versus how the other was done, saying that that’s really not quite a fair fight when we do comparisons. And I essentially tell patients that there’s not much difference, clinically, in outcome between the 2-drug regimen and the 3-drug regimen.

If I have a patient where they’re very symptomatic, a lot of tumor burden, hurting from it, and they’re young enough and fit enough, that’s a patient I’ll try the 3-drug regimen in because I want every percentage point of response I can get in that patient. But for me, and almost everybody else, I’ll tend to use the 2-drug recipe as initial lines of therapy, mainly because I find the FOLFIRINOX regimen, for all the machismo out there, difficult to give to patients over a long haul.

So, in summary, I spend the time, I describe the 2 regimens in detail and so that they have a pretty clear understanding. And then, of course, what happens is the patient says, “Well, what would you do?” And I’m like, “Oh God, I don’t know what I would do.” I then do a gut check and think, what would I do if I was sitting over there? And then I make the recommendation to the patient going forward.

Transcript edited for clarity.

April 2015

• A 66-year—old female presented to her gastroenterologist with jaundice, weight loss, upper right quadrant abdominal pain, and diarrhea. She continued to carry out normal activity but reported requiring rest on most days.
• CA19-9: 2296 U/ml
• Abdominal CT scan showed an expansive lesion measuring 39 × 26 mm between the pancreas and inferior vena cava, below the portal vein. There was enlarged para-aortic lymph node and stenosis of the common bile duct.
• Endoscopic retrograde cholangiopancreatography was performed and the patient was referred for surgery.
• Explorative laparotomy showed the mass to be inoperable because of local vascular infiltration and liver metastases.
• Pathophysiology confirmed pancreatic adenocarcinoma; stage T4N1M1

May 2015

• The patient was started on gemcitabine + albumin-bound (nab) paclitaxel
• She complained of moderate nausea and fatigue for the first 4 weeks of therapy which was managed with antiemetic therapy
• Neutropenia was managed

August 2015

• CT scan shows stable disease
• CT scan showed no residual liver metastases; the tumor in the head of the pancreas was unchanged in size.
• The patient is asymptomatic and continues to tolerate therapy

June 2016

• Patient hospitalized for high blood glucose levels, diagnoses with new onset insulin-dependent diabetes mellitus
• CT scan showed appearance of several new liver metastases
• The patient was started on the FOLFIRINOX regimen