DR PHILIP: 71-year-old male who presented with increasing fatigue, weight loss of 10 to 20 pounds and bilateral ankle swelling. Had an MRI, which showed multiple liver metastases and a 5-cm pancreatic hypodense mass, underwent a CD-guided biopsy, which showed a poorly differentiated adenocarcinoma, CK7-positive, CK20-negative. Our pathologist thought this was compatible with pancreas/hepatobiliary. A serum CA 19-9 was over 100,000. ECOG performance status was 2, as measured by me.

DR LOVE: So you said his PS was 2. Can you talk more about how he looked to you and what you were thinking about, what he might be able to tolerate?

DR PHILIP: One of the most important things about pancreatic cancer is that when you see the patient today, you don’t know what will happen next week. Because that’s one of the things, if you remember from the gemcitabine/5-FU comparison, they had a run-in period for 2 weeks. At the time I saw him, he was maybe — he was a 2, but I had some concern about this patient, who might go downhill faster than I like to see in an average patient.

DR LOVE: What were the symptoms that were debilitating to him?

DR PHILIP: Fatigue was the more important one. He didn’t have any major comorbidities, but certainly fatigue was limiting this patient most.

DR LOVE: What was your sense about his functioning a year previously, his baseline before this started?

DR PHILIP: This was an Eastern European gentleman who has been very active and healthy and typical exercise and everything. So this has certainly been a change in his overall health, which happened over the last 2 to 3 months.

DR LOVE: So Charlie, what would you be thinking about?

DR FUCHS: In somebody with an impaired performance status with pancreatic cancer, if I’m going to pursue any systemic therapy, it’s going to be single-agent gemcitabine.

DR LOVE: Single-agent gemcitabine. Johanna, what would you be thinking about?

DR BENDELL: This is the toughest part, right? Because what’s causing the poor performance status? And I think for Philip’s patient, it seems like it’s his disease. So what I’ve started to do lately — and I’ve been dipping my toe in the water, because I think I used to have very much a stance like Charlie’s, to do the single-agent gemcitabine — but I’ve started to become just a little bit more aggressive in a patient who understands that I’m going to be giving a pretty intensive regimen. And I actually recently had a patient just like this whose performance status was really declining rapidly. And I ended up starting him off on a very modified dose of FOLFIRINOX.

And, of course, N of one, right? But pulled him right out of the fire. I mean, his ascites are controlled. His fatigue is controlled. He’s eating again. He’s feeling well. So it’s that kind of toss-up of, do you try to use the response rate to improve how patients are feeling versus the toxicity of chemotherapy? And I think that’s a very straight-up conversation you have to have with your patient, as well.

DR LOVE: I wonder how often the patient’s perspective on this comes in. What was this man’s attitude? Was he interested in taking a shot at something, maybe that could be a little bit risky, but maybe getting him back on his feet? Or was he kind of just, “Leave me alone”?

DR PHILIP: No. This man was someone who wants to live. And certainly, for that reason, I gave him several options.

DR LOVE: So Randy, again, you have this man who seems to be going downhill fairly fast with pancreatic cancer, wants a shot at something, but, of course, we don’t want to tip the —

DR HECHT: Actually, I’m really glad you chose this patient to present, because this patient is much more representative of the patient that we see in our practice than patients who are on studies. And that’s the problem with extrapolating from studies, particularly the FOLFIRINOX study, which was really a very good group of patients that — this person would never be on a trial. And so I think this is much more likely the person who’s going to walk in or sometimes come in with a walker to my office.

I actually kind of agree with Charlie, and I would probably give the patient single-agent gemcitabine. I mean, I have had excellent responses to FOLFIRINOX with improvement in quality of life and performance status. I’m thinking of a patient I saw last week. I’ve also had some prolonged benefit in quality of life with gem/nab paclitaxel as well. But this patient sounds — I mean, once again, this is the art of laying eyes on the patient. But really, I mean, there are 2s and there are bad 2s. And then there are like 1.5s. But if a person really, really truly were a 2, I would have a harder time giving him combination chemotherapy.

DR LOVE: So I guess nobody here would give ruxolitinib? Just kidding. But when you think about, why is this man ill? Why is he so sick? What’s going on that he — and could part of this, Philip, be some kind of paraneoplastic or cytokine issue?

DR PHILIP: That’s the likeliest thing for someone who was very well for his age months ago and now he’s not doing well. And — but this gentleman, when I looked at him with my experience in pancreatic cancer, he didn’t look like someone who’s going to really be a performance status 3 in a week. So that made me more confident in giving him my options.

DR LOVE: So again, Eileen, as we hear more about this case — I don't know how it’s affecting what you think you might do. Any thoughts?

DR O’REILLY: Yes. So I think it’s a discussion with the patient, what they’re willing to accept and what their goals are as to how intensive the treatment should be. But I would probably strike a middle road here and go with the 2-drug combination, seeing that he was a relatively fit gentleman and probably has one good shot. Three drugs may be too much.

DR LOVE: Which 2?

DR O'REILLY: Probably would give him gemcitabine and nab paclitaxel.

DR LOVE: Interesting. Rich?

DR GOLDBERG: So it’s I think a sign of the improvements that we’ve made in pancreatic cancer that we even have options to give. And we always used to give gemcitabine with a nihilism that we weren’t really going to hurt them, but we weren’t really going to help them, but it was something to do and everybody knew how bad the disease was. Now, you can even contemplate this issue of do-or-die therapy. We’re going to throw the Hail Mary and hope it gets caught in the end zone. And I think if the patient is informed that they’re taking a risk and that they may actually get dragged down by aggressive therapy or they may be resurrected by it, as long as they make the decision to go ahead, it makes good sense. So I would say that a year ago, I would have said gemcitabine or hospice. And this year I would say we have some other options, if you want to go and be aggressive on this.

DR LOVE: And he said, “What do you think? What should I do?”

DR GOLDBERG: I would judge the patient. I would judge the fact that this guy was healthy before, that his trajectory of disease seems to be rapidly downhill and, therefore, it’s his disease that’s hurting him. And when I teach fellows in clinic and I show them a liver full of well-differentiated neuroendocrine tumors and compare it to poorly differentiated colon cancer and poorly differentiated pancreatic cancer, the difference in the way the patients are doing is clearly related to something that the tumor is doing to them, besides occupying space in their liver. And pancreatic cancer, I think, does have this cytokine or whatever it is — I’m not sure we really understand what it is — that makes people anorexic, makes them fatigued, makes them really distressed. And if you can reverse that quickly, you can pull them back from the edge.

DR LOVE: So what specific regimen do you think you would likely to be using?

DR GOLDBERG: I would give the person a choice between single-agent gemcitabine and FOLFIRINOX in this setting. And I probably would dose reduce the FOLFIRINOX a bit in the first cycle.

DR LOVE: I didn’t hear nab paclitaxel in your answer.

DR GOLDBERG: I’ve not actually given nab paclitaxel. And I have to say that the fact that it’s a gemcitabine-based therapy gives me less confidence in its resurrection powers.

DR LOVE: So I’m curious just from a practical point of view, Charlie, I mean, why would you not add nab into gem? Would you be concerned about toxicity in this man?

DR FUCHS: I think the point that’s been made by several folks here is you have to see the patient. Right? The bottom line is, the trials that we’re talking about don’t apply to somebody who’s ECOG 2, because they could not be enrolled. And so I think if in your clinical judgment you think this is somebody who’s ECOG 2 but isn’t rapidly deteriorating and is, in fact, ECOG 2 because of their disease and potentially the response will resurrect them, then sure, I think you could be contemplating adding nab paclitaxel to gemcitabine or doing some dose-modified FOLFIRINOX. And the devil’s in the details. You’ve really got to see the patient.

DR LOVE: Yes. I was thinking when you talked about the modified FOLFIRINOX, what they call RVD Lite in myeloma now for the older people. They give them the same regimen, they just start real low and start to go up. Randy?

DR HECHT: But the differences are — you brought up hematologic malignancies like ALL and things like that, or even myeloma. Those patients do much better. And so what you’re talking about is that if you win, then you’ve won a bit. Or at least with allotransplant — or maybe in myeloma, you’ve hit a double or something. And what we’re really looking for — I mean, even the best option for this guy — whatever, if he does well, the chance of him being alive a year from now is really small. And the chance of him being alive 2 years from now is real small. So I don’t want to oversell even though we’re always happy when people have responses. I’m very happy when the patient feels better. And we all have patients like that. But I think we have to understand what the long-term outcomes for these patients are as opposed to hematologic malignancies, where you’re willing to push harder because the benefits are greater.

DR LOVE: Although, again, putting myself in this man’s position, maybe I’d be thinking to myself, “Wow! If I could just feel good again for 6 months, it would be incredible,” even if I did end up dying in a year. And anyhow, maybe just briefly you can talk about what happened.

DR PHILIP: Just briefly, he did have a DVT just before we started treatment, so we put him on the low molecular weight heparin. I did give him 3 options of gemcitabine versus gem/nab paclitaxel but also modified FOLFIRINOX. In my practice, I do the UGT1A1 routinely, and I modify the dose of the irinotecan accordingly. I do that in all my patients. So that gives me a bit more control over the irinotecan.

He chose to go on gemcitabine and nab paclitaxel. His albumin start was 3.1. That, to me, is another very important thing I look at in my patients, including the absence of ascites. After the first 2 months of treatment, he got a CAT scan, which showed stable/possible improvement, but after 4 treatments he started to have progressive disease.

Colorectal cancer

Gastric cancer

Pancreatic cancer

Hepatocellular carcinoma

Gastrointestinal neuroendocrine tumors

Gastrointestinal stromal tumors