Meet The Professors: Pancreatic Cancer Edition, 2016 - Video 1765-year-old man with a history of Type 2 diabetes discontinues treatment with FOLFIRINOX for mPAC because of poor tolerance
9:22 minutes.
TRANSCRIPTION:
DR GLYNN: So this is a 65-year-old gentleman who had just retired, family was intact. His daughter was a nurse. He had extended family, very involved. And he came in to see me, actually, in second opinion. He had, at the time of his first opinion, a pretty good performance status, even though he had significant weight loss. He had some nuance of abdominal pain over the course of a couple of months. And so we talked about treatment options. And we talked about FOLFIRINOX. But also, he had a CT scan that had shown hepatic metastasis. There was involvement around the duodenum. He had a very high 19-9. And so we also had this discussion of there’s a range of options here, which would even include palliative care, which he really didn’t want to hear about. And I don’t think at that moment it was so unreasonable that he didn’t want to hear about it. DR LOVE: Can I just bring up 1 issue here? What was his treatment prior to his weight loss for diabetes? What happened to his diabetes when he started to lose weight? DR GLYNN: His medical comorbidities were quite stable. DR LOVE: Margaret, any comment about diabetes in pancreatic cancer, the link and what it might be and also, your experience with patients who have, say, insulin-dependent diabetes, who are losing weight, that glucose control? DR TEMPERO: This is a big issue, diabetes. And it’s a complex issue. Diabetes, long standing, is a risk factor for the disease but a mild risk factor. DR LOVE: Association? Is it thought to be more of an association or causal? DR TEMPERO: No. It probably is a true risk factor, probably with insulin driving IGF1. But, short-onset diabetes, that is caused by the cancer. And the pathophysiology of that is not well understood. DR LOVE: It’s not a replacement thing, that — DR TEMPERO: No, no. The islets are not destroyed. We’ve been able to demonstrate that there’s insulin resistance. There’s also a little bit of perhaps less insulin being produced, but it’s a very complex thing. And it may be a paraneoplastic syndrome. DR LOVE: And how do you manage it? DR TEMPERO: Generally, when you treat the cancer effectively, it gets better. But if not, you manage it like any other case of diabetes. DR LOVE: But with insulin? You said it was insulin resistant. DR TEMPERO: In some cases, you can manage it with insulin. DR LOVE: Could I just ask, Mike, have you see this? How often do you see this, incidentally, clinically evident diabetes? DR TEMPERO: Clinically, I would say about half the patients. DR LOVE: Half the patients! Mike, do you see that? DR SCHWARTZ: Absolutely. DR LOVE: Really? Do they present with it? DR SCHWARTZ: Yes, they present with their diabetes, either being diagnosed with diabetes at late age or hard-to-control diabetes that was previously well managed. DR TEMPERO: Yes. DR LOVE: So he is struggling with the first-line choice that we’ve been talking about. What did he end up getting, and what happened? DR GLYNN: So he ended up getting FOLFIRINOX. DR GLYNN: And he did terribly on FOLFIRINOX. He had terrible diarrhea. He was sick. He required a hospitalization and basically came back and said, “Find another regimen. This is not worth it.” DR LOVE: How many treatments did he get? DR GLYNN: He had 2. Two in total. DR LOVE: How often do you see this, Margaret, and any association? Would you have predicted this? DR TEMPERO: I would say maybe about 10% of the time, even a hospitalization or at least a trip to the ED happens. DR LOVE: That’s FOLFIRINOX specifically? DR TEMPERO: Yes. And one of the things, the way we try to preempt it, these patients can get very dehydrated with nausea and vomiting and diarrhea and so on. So many times we bring them in routinely for hydration after they’ve been treated. So 2 or 3 days, just bring them in routinely, make sure they’re getting hydrated. And obviously you’re spending a lot of time, and I have the most awesome nursing group in terms of palliative management and supportive care management trying to get their antiemetics in control, their antidiarrheal medications as optimized as possible. DR LOVE: Yes. It’s always easy to second guess, but just looking back at this 65-year-old patient, would you have likely used FOLFIRINOX? And is there an age where you really start pulling back? DR TEMPERO: I’m not hesitant at all to use FOLFIRINOX, because I know we’ve got a good supportive care network to manage these patients. And their most severe symptoms are going to be during the first cycle. You’ll get a little bit better in the second cycle as their disease improves. As their disease is getting under better control, it gets easier and easier and easier, so pretty soon. You can coach a patient through this. And pretty soon you can get them on an even — smooth waters. DR LOVE: Okay. So he had these problems. He recovered completely? Or not? DR GLYNN: Yes, he recovered and was still eager for treatment and went on to gemcitabine and nab paclitaxel. And it was a whole different thing. He tolerated it. I’ve met with him a couple of times. He still sees my partner in the other office, but I’ve seen him a couple of times. He looks great. His performance status is excellent. His 19-9 went from 18,000 to 200. And he looks terrific. DR LOVE: And that’s his current status? DR GLYNN: That’s his current status. DR LOVE: What’s his state of mind? DR GLYNN: He’s a highly intelligent guy. He’s a former English professor. And he’s got a very realistic idea of what’s going on, that this is going to hopefully last for a while but it’s not going to last forever. DR LOVE: Is he the kind of person that would be willing to go to an academic center for a trial? DR GLYNN: Yes. DR LOVE: What do we know about sequencing and responses, people who don’t respond to 1 and respond to 2, both ways? DR TEMPERO: If I could maybe offer a counter case but not so dissimilar, a fellow that came to see me being treated by an outside physician, who had been on about 2 months’ worth, so 4 cycles, maybe a FOLFIRINOX, was miserable. He was miserable. And this was a very difficult case to dissect in terms of whether he was getting any benefit, because he had metastatic disease but only found at the time of laparoscopy. So his disease was radiographically occult and he did not express CA 19-9. So I had only his symptoms to go on. And he said, “I’m so miserable. I don’t know if I feel any better.” I said, “Okay. We’re going to take a 1-month break from treatment, and when you come back you’re going to tell me how you feel compared to when you were diagnosed.” He came back in and he said, “I feel great compared to when I was diagnosed.” I said, “That means that what you were getting was helping you. So let’s figure out how to give it safely/comfortably for you.” He went on to receive a full 6 months’ worth over 7 months of treatment. And we took him off treatment. He is now in remission a year and a half later. So my point here is that — DR LOVE: Although we don’t have any objective — DR GLYNN: Right. DR LOVE: — information at this point. DR TEMPERO: He hasn’t progressed a year and a half off treatment; unmaintained remission, that’s pretty good. So my point here is that when a patient has invested in something, it’s up to us to try and figure out how to sort it out and make sure that that investment is fully realized, because when you switch early on, you’re pretty much cutting off — now, you could say you could go back to that treatment at some point down the road. DR LOVE: Tony, again, 65-year-old. Is there an age where you start pulling back just based on age from FOLFIRINOX? DR BEKAII-SAAB: We don’t have good safety data on patients who are, say, 76 or older. So typically the cutoff would be around 75. But that doesn’t mean I wouldn’t treat the patient who’s 77 with FOLFIRINOX, if they’re incredibly healthy and strong. But I’m very reluctant to go above 75. In fact, I’m very reluctant to go above 70, in many ways, with FOLFIRINOX. The only times where I actually use FOLFIRINOX with a little bit more loose criteria is in the neoadjuvant setting, where I know I’m going to limit it to 2 or 3 months max rather than 6 months or longer. DR GLYNN: So Tony, I’ve just got a quick question. DR BEKAII-SAAB: Yes. DR GLYNN: What would you do next with this guy? So this is a patient who technically has not failed irinotecan or 5-FU. DR GLYNN: Right. DR BEKAII-SAAB: And so the next line of defense would be, naturally, 5-FU, nal-IRI or even FOLFIRI would be reasonable, probably not FOLFOX. DR GLYNN: At what point would you consider sending them somewhere to get gene profiling? DR BEKAII-SAAB: I would do it now. I mean, I would do it as soon —We have been doing this, I’d say, semiautomatically. It’s not automatic. But for most patients if not all, we’re trying to profile them. DR LOVE: Margaret, what about the choice for next therapy, agree? In this patient, what would be next for you? DR BEKAII-SAAB: Outside a clinical trial. DR TEMPERO: Outside of a clinical trial, I agree with Tony. I think that would be a great choice for liposomal irinotecan and 5-FU/leucovorin. DR BEKAII-SAAB: Right. Yes. |