Managing Symptoms and Side Effects in Pancreatic Cancer

John Marshall, MD:The patient in our case, 66 years of age, she’s feeling her cancer. She has got pain, she has obviously got jaundice. We’ve got to fix our jaundice, right? Any of our regimens, whether it’s FOLFIRINOX or nab-paclitaxel/gemcitabine, we have to get that bilirubin down to safely administer it. So, on some level, we’re waiting on that. She does have pain. This would be a good case for maybe a nerve block, too, as you’re thinking about waiting on these patients to recover their jaundice.

But her performance status is falling. She has lost weight because of all of this. You want to reverse that; you want her feeling better. She doesn’t have a huge tumor burden. It’s not like she’s full of cancer. She has actually got relatively small liver metastases, relatively small primary metastases. And so, our goal here is reversing her cancer. You’ve got 2 tools that are very similar. I always worry about patients like this, in giving them 3-drug cocktail FOLFIRINOX, of actually making their performance status worse. You want to make them eat better, that they feel better, that they gain weight. So, in a patient where I’m in for the long haul with systemic therapy, I like the 2-drug cocktail because it’s more likely, in my opinion, to improve their overall performance status because the chemotherapy doesn’t beat them up as much. In this patient, her marginal performance status, or falling performance status, loss of weight, pain, etc, make me lean more toward the 2-drug regimen than the 3-drug regimen.

The 2-drug cocktail, the gemcitabine/nab-paclitaxel, I mentioned is a pretty easy regimen to give. The standard dose of 125 mg/m²of nab-paclitaxel and 1 g/m of the gemcitabine is doable in almost everybody. I always wonder why anybody would give single-agent gemcitabine anymore because the 2-drug regimen is more effective and essentially just as easy to give. The big barriers you run into with the 3-weeks-on/1 week off schedule is myelosuppression. Yes, there’s minor nausea that’s pretty easy to cover. You don’t even need big gun antiemetics for it though. There is fatigue, as is common with most chemotherapies, but it’s not bad. And then, you have some of the rare side effects, allergic reactions and things like that. Hair loss, probably the biggest thing that upsets patients, does clearly happen with both regimens, but probably more with the nab-paclitaxel.

My biggest struggle with the regimen, honestly, is counts. And getting those 3 weeks in a row at full doses in Washington, DC, in Georgetown, seems hard. It’s not uncommon that we’ll have to hold that third week. And everybody has different strategies for managing that. I think a very popular strategy is keep the doses full and go to every other week, which is nice on your patients as well. But I will tell you, I set out with a 3-weeks-on/1-week-off schedule and see how they do. Then, I tell patients right from the beginning that this may change over time, depending on how they do, partly, particularly in this patient, because I want her symptoms to improve. So, I don’t want to be too kind, too gentle up front. I want the drugs to work, I want to get them. But that’s more or less how I manage it. And I will typically see patients at least every other week when they’re on that. So, I see them at the beginning of the cycle and on week 3, until I really know they’re on a nice plateau. I then start seeing them only about once every 4 weeks.

The patient that presents had diarrhea. Why did she get diarrhea? And one of the things that’s a very common thread, that we often miss in clinic, is malabsorption. So, when you have pancreas cancer, particularly with a blocked bile duct or if we’ve radiated these people or operated on these people, their pancreases are not making enough enzymes to absorb fats and proteins. This is one you ask the spouse: are they passing a lot of gas? Is it pretty stinky? The spouse is over there going like this, that if you take a good history, you can find malabsorption. And so, we can fix malabsorption through the enzyme replacement. Look for this in a supportive care setting for our patients. We watch their sugars because these are people that can get some adult onset diabetes because of what we do to their pancreas during all of this treatment.

Pain management is critical in this world, and we often forget nerve blocks. They’re relatively simple to do. Our IR guys and GI guys like doing them. And so, we need to make sure we use our allied professionals to help with overall symptom management. And then, I would say nutrition support is critical. These people are struggling to keep their weight. They have the malabsorption issue; they might have diabetes. So, bringing in nutrition support is really, really important as well.

I encourage our patients to keep moving. We really want physical activity as much as possible. Keep their heads up, keep smiling, have a plane ticket. Really address their social/emotional needs because what I think we do too often as oncologists is we pin our patients down to our clinics: “We want you on time and precise, and we’re never going to miss a treatment,” etc. That’s really not true. We need our patients out there living. The reason we’re working on their symptoms and the reason we’re treating their cancers is so they can keep living, and so we need to encourage them to do that as well.

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