ToxCheck: Managing Side Effects of Pancreatic Cancer Treatment

Intro Hello and welcome back to another episode of the Oncology Brothers Podcast. I'm Rahul Ghosain here with my Co host and brother Rohit Ghosain. We're excited to continue our talk check series where we discuss managing the side effects of the drugs we use day in, day out in our clinics. Today, our focus is on pancreatic cancer. This is a tough disease to begin with, so keeping our patients on these treatments for long duration while keeping the quality of life in mind is important. We'll cover a lot here from 5 FU to liposomer no Tecan to gemnapaclotaxel. And to walk us through this and touch in some clinical pearls of these agents, we're joined by Doctor Rachna Shraf from the University of Arizona and Doctor Mithunmala from University of Alabama. Rachna and Mithun welcome. Speaker 2 Oh, welcome, Russian and Mithun. So let's dive in as we have quite a bit to cover. Starting off with five FU, this particular drug has been heavily utilized in GI space and other malignancies. 5FU Rachna, even before we start talking about the common side effects, any utility of five FU Bolus and Leucovorin, what is your practice like? Speaker 3 Yeah, I think that's a great question. Do we really know? I don't know that we know. But what I will say is I have a tendency and keep in mind, I treat primarily pancreatic and biliary malignancies. And you know in the world of pancreas, we we do full fury knocks and it's a it's a tough regimen. And so most of us modify full fury knocks. And I would say that that in almost all of my patients, I tend to eliminate the bolus 5 FU as well as the Leucovorin. It's really to mitigate the toxicities that can sometimes be overlapping between that regimen of full Ferrinox. Speaker 2 And Amitan, what is your practice like there? Speaker 4 I I see Algi with predominant focus on colorectal and hepatibilia in the metastatic setting. I agree. Do not use the five FU bolus or the Leucovorin bolus. I think there is a JNCCN paper that was published recently in September that did a huge, like a large retrospective analysis, 18,000 patients, no difference in survival benefit. I think that also supports the practice that I do already in the curative setting. I think I should say I'm a little bit hesitant because of the curative setting, but I give them perhaps one or two treatments and you know if there's really challenging with the toxicities that they have with the five FU bolus neutropenia compromising their next ability to tolerate, I mean to receive the next cycles of treatments, I think I'll have very low thresholder. Speaker 1 Topic OK, so No 5 FU bolus Rachna, the test for DPD deficiency upfront for all your patients. DPD deficiency testing You know, this is a question that I've been asking myself. It is not been my standard practice and a lot of it is just related to the turn around times and things like that. But you know, it takes just one experience to make you feel like this is something that we need to be doing a little bit more standard. I don't do it across the board, but I have been using it and do it testing for it a little bit more regularly. Speaker 1 And more than so we have consensus of No 5 FU bolus, but that means we're using 5 FU lung infusion. What are some of the key side effects that we have to keep in mind? Common side effects of 5FU And importantly, how can we manage that, be it with five FU? And also let's touch a little on Cape site to Bean as well. Speaker 4 Yeah. No, absolutely, Rahul. I think that's really important to know with the five FU. Yeah, I think it all comes down to the mechanism of action. 5F you really impacts the cells that are rapidly dividing, and in our body that rapidly dividing cells are present from the mouth all the way to the anus. The common side effect we see is mucositis, the diarrhea. These are the most common side effects. We see the infusion. In addition, you could see nausea or vomiting as well. That depends on the dose and the sensitivity of the patient, but these are the common side effects. So piggyback on the question of the Xeloda, I think it's side effect profile is little bit different than the 5F you, although for the most part they're similar, but we tend to see a little more palmar plantar erythroidis aesthesia, the so-called hand foot syndrome, which is commonly seen. Then we do have this rare side effect, the coronary vesospasm. So I do have some patients experience and this is becoming more common as we learn about it. I think that's important, but important to, you know, pay attention to as well. Speaker 2 Thanks for touching on that coronary vasospasm. Coronary vasospasm With regards to coronary vasospasm, which we see more with continuous infusion as opposed to bolus. If one is experiencing that, what is your practice like? Switch them to bolus. Use that weekly regimen with oxaliplatin or with our NOT can. Speaker 3 Yeah. I think my first preference is to get cardiology involved and to see if with the use of things like calcium channel blockers, nitroglycerin and things like that, if we can mitigate it. Because as we just alluded, I do think that continuous infusion from a mechanism of action perspective in terms of the diseases that we're treating, there is something really important to it, but that's possible. I work with my cardiology buddies and I try my best to offset it. If not, then yes, some of the other alternatives you mentioned are all on the table. But the other thing to remember is Zoxali Platin has nothing to offer without the five FU. Reno TCAN does have single agent efficacy. So if things get really tough, that could be something to think about as well. Speaker 2 Thanks for highlighting that. As Mithun also mentioned, Cape Cider Bean keeping side effects like diarrhea, mucosidis, hand foot syndrome or extremely important and dose reduction with two weeks on, one week off along with that is extremely important with Cape cider bean now moving along into oxaliplatin space. Managing side effects of oxaliplatin Even before we touched on Oxaliplatin, the minute we're talking about Cape Cider bean, I think Voltaren gel makes a world of a difference. Speaker 2 Right, a cheap alternative, but again, very, very effective. Now focusing on oxaliplatin, we have to keep in mind the neuropathy, cold sensitivity, limiting exposure by dose reduction and then eliminating oxaliplatin in pancreatic cancer or colon cancer is often what we do. Rachna, any tricks in managing some of these side effects? Does cryotherapy or acupuncture actually works? Or relying on gabapentin and pregabalin is the only choice? Speaker 3 Yeah, You know, I think the interesting thing that I found is that different things work for different people. When we're talking about curative versus metastatic, the questions of eliminating the Oxali dose, reducing the Oxali come into play. I'm a lot harder pressed if I'm giving adjuvant FOLFIRINOX to try to get rid of the Oxali platen. So that's when I, I try a lot of different things and I try to be a little bit more preemptive rather than reactive because by the time they're at the point where that neuropathy is a grade 2 or grade 3, being able to reverse it or prevent it from progressing is a lot harder. And so, and I mean, I use pregabalin, I use gabapentin, I use duloxetine. You know, I think that actually has some efficacy as well. And then I have had some patients who have had some incredible benefits from things like acupuncture and. Speaker 1 Just this week, we actually saw data from JAMA focusing on paclitaxel compression and cryotherapy had some effects for neuropathy. Of course, we'll touch this again when we're talking about GEM, not paclitaxel. Neuropathy ends up being a very big issue when it comes to quality of life. That's on Any additional thoughts around Oxaliplatin I? Speaker 4 Completely agree Neuropathy is a make or break for the oxaliplatin treatment in my patients and holding on the point Dr. Schroff mentioned in terms of like preempted and and for the reason I also tell my patients there is nothing approved for this management. Additional thoughts on Oxaliplatin You have a good phase three data that supposed to Cymbalta seems to be beneficial. But again, in my patient experience, some patients it works, some patients it does not. Some patients I saw Cymbalta, they come back with hallucinations or dizziness or some side effects, they can't take it. The others do. So I try to use a menu or a plethora of options. I even ask them, OK, try 123. Physical therapy is another option that helps acupuncture and that sort of stuff. The other additional side effects I've seen in my practice are hyperpigmentation of the skin, especially the fingers, and taste alteration along with the sensation when they're eating food the longer they're on. A few of the things that helped, of course, in addition to dose reduction. And this sounds a little more vague, but I think I've tried them to brush their teeth before they eat food and that seems to help. And baking soda rinses seems to help that oral discomfort for my patient who really needs Oxali but at the same time they're having the side effects. Speaker 1 Oral discomfort is actually a phase two data for oral chips while you're getting oxaliplatin, just oral cryotherapy. So another little clinical Pearl, small study, it's a phase two, but something relatively benign to keep in mind. All right, so then on to irinotecan. Irinotecan I acknowledge we're moving through this fast with irinotecan. We have to worry about diarrhea, which can be problematic and early onset or even late onset. And we also have to keep marrow suppression in mind. Netherland, any clinical pearls when it comes to Irinotecan? Speaker 4 So, yeah, I mean totally, I think you don't know T can. One of the common side effect that I see in my practice is nausea, vomiting stands out along with the diarrhea. It's used quite predominantly in our practices. In the metastatic setting, I tend to even start with 150 milligram per meter square rather than 180 milligram per meter square. I also like to check in addition to DPD, UGT 1A1 as well. With my personal experience in my previous institution, we tested about 250 plus patients and interestingly 13 to 15% of them had EGT when homozygous 28 variant and then about 38 or 40% of heterozygous. The ones who are homozygous, they have a lot of side effects to tolerate heterozygous. It's a hit or a miss full dose, this is 80% dose reduction. So that's something I tried to do in my practice. Those are some of my experiences. Speaker 1 Nathan, are you doing that for liposomoronotecan? Are you testing that out front for liposomoronotecan as well? Speaker 4 When when it initially came out and improved, I all honesty, I used to do it, but I think I saw more recently, you know, an abstract that came out of Asco GI that they tried to do that study by checking UGT when A1 and Nana in this in that, you know, nano like T can doesn't seem to have much of A impact one versus the other. Maybe it's because of the lower dose being used there. So I I feel more comfortable not testing it with that data. Speaker 2 Educating patients on what to expect, giving clear guidance with regards to antidiarrheals does go a long way. And as Mithun and Rushna, as you mentioned, being proactive rather than reactive is the key. Well, up next we have here is liposomal iron or Tecan, which got approved initially in second line space and now even in first line setting for pancreatic cancer. Liposomal RNA Tcan It was rather I think earlier this week Doctor Tony Bekasab where tweeted about a patient friendly plain language summary for Napoli 3 comparing Naliri Fox to GEM Napaclitaxel. Now can we talk about liposomal RNA TCAN and then it'd be good segue to GEM, Napaclitaxel, Rachna, liposomal arena. Tican made its name in pancreatic cancer for better tolerability. But none of these drugs as we know are benign. But diarrhea and fatigue is still a concern, though neutropenia is slightly better. Any clinical pearls here? Speaker 3 Yeah, I agree. It's funny to me that this was heralded as a as an easier version of Irina Tican. My experience has been that the diarrhea can be really tough to control diarrhea. And you know, again speaking to preemptive and I give all of my patients very clear instructions on Imodium and Lomotil and you know, just exactly how and when to start and low threshold for beginning basically around the clock anti diarrheals so that we don't end up chasing our tails. Sometimes this becomes a tough cycle to break. People become dehydrated and we're dealing with the hypokalemia and all the other things that come from significant diarrhea. I don't necessarily think it's every patient. It's not been something where 75% of my patients are getting leery are ending up with this significant diarrhea. But somebody once told me related to the FGFR inhibitors and Cholangio, we grade things and say, oh, it's just a grade 2 diarrhea. But a grade 2 diarrhea in terms of quality of life and impact on the patient is actually quite dramatic in terms of the number of bowel movements and the impact it has on the body and nutrition. And so that's been my take home for an oleary make sure the patients really understand how to manage that diarrhea very, very actively. Speaker 2 Stress the importance of quality of life, especially when you're talking about palliative treatment. Smith and while talking about the Imodium and Lomodel. Liposomal iron How do you handle it? Your thoughts on liposomal iron as he can. Speaker 4 Yeah, first, thanks Raja for stressing that grade 2 is not easy, it's not fun. I I personally don't want to see myself doing it. One of my biggest pet peeves with management of Imodium is a lot of patients don't know that they can take up to 8 tablets of Imodium per day. A lot of them take one or two, anything that's enough for the day. I'm worried about Constipation sometimes. But my key education right from the get go for them is, you know, I even sent prescriptions for Imodium because in my experience I feel a prescription versus an over the counter medication, there is a difference in utility. That's my personal opinion. And there's more chance of picking it up from pharmacy. So I give both Imodium and Lomotil. I tell them clearly you can take 8 of them, you still need lomotil. Stay on top of it and take them. But when things get worse I think stopping treatment for a site makes sense right? Imaging can also show signs of colitis. I've had few patients have colitis. I tend to use Cipro Flagyl for 10 days or like a week or so. They feel much better with abdominal discomfort and colitis after using it and resume the cycle back up again. So that has been my experience. Speaker 1 And I'm going to start using that track of sending a prescription rather than relying on over the counter. It makes sense. You're sending something and you're hoping that they're going to be more compliant with this. Again, we're focusing here on diarrhea, though the side effect of marrow suppression. Is that better? That should still be on our radar. OK, now on to GEM and Napaclotaxel. GEM and Napaclotaxel On our boards, we often get tested TTP like picture with GEM cytobine or atypical HUS with not paclotaxel. Of course, we have to worry about neuropathy again, fatigue with this combination. And we also have to be careful with patients that have elevated bilirubin when you're using this combination. Rich, know your thoughts here. Speaker 3 So yeah, no, I agree. I mean, you know, I, it's funny because when Fufirinox and Gemnapaclotaxel first, we're being constantly compared head to Ed, everybody was like, oh, full ferrinox is so toxic and gemnab paclitaxel is so much easier. But I have to be honest, I don't use the impact dosing like the phase three dosing of gemnab paclitaxel because I think that if you do give it in, you know, days 18 and 15 of a 28 day cycle, the mile low suppression that you're dealing with, inevitably patients miss the day eight. I have a tendency to give it every 14 days. You know, Speaking of Tony Saab, I mean a number of people have published data to demonstrate there's really not much difference in efficacy, but much better management of toxicity. How to manage side effects of GEM-NAB paclitaxel One thing we've learned is with a lot of these drugs, the dose limiting toxicities limit our ability to use these relatively active agents. This is still pancreas cancer. But if we have to drop the Nab paclitaxel due to neuropathy or keep missing doses because of myelosuppression, just like with FOLFIRINOX and and some of the other side effects that come from that, I I think we're doing the patient a disservice there. How can we keep this going and manage those side effects properly and in a preventive manner so that you can keep them on GEM NAB paclitaxel as long as it's working? To me, the dual issue between the GEM and the NAB paclitaxel in terms of myelosuppression like the thrombocytopenia and neutropenia in particular is one of the biggest issues. That's why I give it every 14 days. It it ends up allowing me to not necessarily need growth factor support typically and and it's just is able to keep them on a little bit more of a of a rhythm. Speaker 1 Absolutely. And just before we close Ruch, not anything to add for community oncology when we're facing pancreatic cancer or giving these drugs most of our patients in this situation, our goal is palliative intent. Speaker 3 One other toxicity that we didn't mention, but I feel like I've been dealing with more compared to my junior faculty MD Anderson days is the the pneumonitis. Pneumonitis You know, both chimp cytopine and abaclotaxel can cause a pneumonitis. It gets a little tricky to figure out which one is causing it, which is also difficult in terms of management and and what to treat them with. I have this running theory that I've yet to validate here in Arizona because of Valley fever. I just wonder if people have this kind of underlying pulmonary microenvironment that is predisposing them to this because I feel like I see it so much more now than I did in Houston. I do think it's an important toxicity that can really go from bad to severely bad very quickly, and it's something that we always need to keep an eye on. Speaker 2 Thanks for mentioning that, and with regards to we know that gemcitabine is still an active agent without NAP paclitaxel in an elderly population, do you usually rely on starting gemcitabine as a single agent and then add nap paclitaxel later on? Gemcitabine To me, AJ ain't nothing but a number. It's more of a performance status based thing rather than an age thing. Every 14 day gem. Napaclotaxel is quite manageable and tolerable. There have been times where I will start them on single agent gem. Once they prove they're doing okay, you can sometimes ramp up an add in the Napaclotaxel. That's been my typical MO. I don't know about you, Mithin. Speaker 4 Yeah, I do agree as well. Performance status Trump's in that situation. We can have me other day. I've seen an 81 year old really fit female. I felt like I wish I could be like you and I become it really important if you're using day one. Day 15, I skip day 8 all the time for elderly. I try to even start with 80% dose reduction right off the bat if it is in the palliative intent. I talked to my patients. We are in a marathon. We just need to take things slowly so we complete the marathon or at least go as close as we can, right? As of yesterday, I found an international study that compared GEM Nebula to Axle day one 815 versus alternating GEM and Abraxane. They found not much of a difference. So I don't use it in the practice. But that also helped me reiterate one more time that, you know, even if you alternate the treatments, once you give GEM, once you don't, that seems like it doesn't have a lot of impact on overall survival. Overall, I favor performance status and other factors as discussed. Speaker 2 Indeed, the conclusion is age is just a number certainly relied on performance status as the key and striking the right balance between side effects and ongoing efficacy when treatment is palliative and not only for pancreatic cancer, but for any metastatic disease is extremely important. Rushnet and Mithun, thank you so much for sharing your thoughts and insights around some of the most common drugs we utilize in pancreatic cancers. For listeners, let us go or a quick recap today with doctors Rushnatraf and Mithunmala, we focused on side effect management for pancreatic cancer drugs, including five FU, oxaliplatin, irinotecan, liposomal irinotecan and the combination of Gemnet paclitaxel. The discussion was not Tubolis versus Tubolis for five FU bolus, I'm utilizing that in curative intent along with lukevorin, but not in metastatic space. With regards to limiting oxaliplatin usage is extremely important because of neuropathy concerns. Speaker 1 The other thing is when we're not using 5 FU bolus, Leucovorin has very limited role. And we also touched on irino tcan. Keeping diarrhea with this in mind is going to be important. And then we also touched on liposomal irino tcan. Though this is better tolerated, GI side effects should still be on your radar. Yes, this is better on your marrow but you still have to monitor your cell counts closely. To close, we talked about GEM, Cytobine and Napaclotaxel where TTP or atypical HS like picture is rare but you should keep that in mind. Another rare side effect that we touched on was pneumonitis and of course with this combination peripheral neuropathy. Thanks for tuning in. Make sure to check out our other toxic episodes on antibody drug conjugates, CAR T and anti EGFR drugs used in colorectal cancer. See you next time we are at the Oncology Brothers.