Classification of Emetogenicity of Chemotherapeutic Agents

Lee S. Schwartzberg, MD: Let’s talk about the guidelines. We have great guidelines, now, from MASCC , NCCN, ASCO, and ESMO. They’re all very similar. Can explain a what we call “highly emetogenic chemotherapy,” and the other categories? What do they really mean?

Dawn Dolan, PharmD, BCOP: Sure. This has morphed over the years. It used to be graded based off of levels. Now, our coin phrases are HEC [highly emetogenic chemotherapy] and MEC [moderately emetogenic chemotherapy].

Highly emetogenic chemotherapy is typically considered inducing nausea in greater than 90% of the population if you were to not give any prophylactic antiemetics. It will universally cause nausea and vomiting, even with very low doses. That was one of the good things that the guidelines did a couple years ago—they reclassified cisplatin. Instead of those lower doses kind of being the MEC, now any dose of cisplatin is considered highly emetogenic.

Moderately emetogenic is a really difficult category for us. That’s a much broader category. It’s between 30% to 90% of inducing emesis if you were not to give antiemetics, so it’s a really big range. That’s one of our harder areas. And one of the nice things that we’ll talk a little bit more about later is that, this year, they reclassified carboplatin and jumped those higher AUCs [areas-under-the-curves] into a highly emetogenic chemotherapy range, versus the moderately emetogenic chemotherapy.

Lee S. Schwartzberg, MD: Beth, you give a lot of carboplatin. What’s your experience with carboplatin?

Beth Eaby-Sandy, CRNP, OCN: I think my experience is 30% to 90%. This drug is difficult because some people do very well, and other people do terribly with it and have a lot of nausea/vomiting that lasts. I typically think of carboplatin and day 2, day 3 nausea, but some people get it for 5 days. This drug has been, typically, hard to predict, and I would say that there’s a good chunk of people that get a lot of nausea/vomiting from it. So, I think classifying it in the high category gives us the ability to pre-med appropriately.

Howard Levine, PharmD: I have a little bit of a problem with the way the categories are laid out. 90%, or more, is highly emetogenic, whereas 89% is not. Now, you’re going to tell me that we could find that difference? And it goes back to trying to define patients better. Who is more likely than not? 30% to 90%—come on, it’s just so big a range that I can’t make heads or tails out of it. When we looked at FOLFOX [folinic acid, fluorouracilf and oxaliplatin], for example, we said, “Oh, it’s 40%.” It really is 40%, and we try and tease out who needs help up front rather than waiting for them to come back at cycle 2, where they’ve already had a bad experience. I appreciate why these regimens were stratified in this way. I’m not sure it’s particularly helpful, and, again, it leads people into believing something which may or may not be true on an individual basis.

Lee S. Schwartzberg, MD: I think it’s a really important point. These categories were the first attempt to try to make some sense out of something we didn’t know. And 25 years ago, they were really excellent. They’re still based, as you’ve all said, on not using antiemetics, which we never do anymore. And by trying to stratify them into very discrete groups, as you’re talking about, this really minimizes this continuum. Things have also changed as to what we’ll accept in oncology. So, to your point, are we really going to accept 40%? Is that acceptable to have 40% CINV when we have drugs that could potentially reduce that? Even if you’re at the low end of MEC, you could make a good argument that you want to use the best prophylactic regimen for CINV as possible.

Howard Levine, PharmD: I always say it’s 100% in that patient.

Lee S. Schwartzberg, MD: 100% in that patient? Even low is 10% to 30%, and yet we’re still accepting that. Now, I’m not trying to make the point that we shouldn’t use the guidelines. The guidelines are useful, but the way we think about supportive care is changing, just the same way we think about what a clinically beneficial response is. We’ve accepted higher criteria now, and we should accept less symptomatology, I think, in the future. That’s something that we should talk about.

Eric Roeland, MD: And these categories were originally set up by vomiting only.

Lee S. Schwartzberg, MD: Right.

Eric Roeland, MD: Which we’re doing much better at controlling. The issue, now, is nausea, and how we’re doing a better job of controlling nausea.

Dawn Dolan, PharmD, BCOP: For sure. When I talk to patients, that’s probably one of the biggest education points—separating nausea and vomiting. Usually when you vomit, you feel better, at least for a short period of time. It’s that chronic nausea. I even try to bring it home and give them a little bit of an empathetic factor: “I’ve been pregnant for about 20 months of the past 4 years, and I was nauseated 100% of that time.” And so, I can empathize with them a little bit by feeling their pain and trying to help prevent CINV—really giving them the best drugs we can up front.

Lee S. Schwartzberg, MD: With carboplatin now classified as highly emetic, how do we ensure that the electronic medical records that we use are updated to reflect this? Dawn, how are you doing this at your institution?

Dawn Dolan, PharmD, BCOP: We conveniently just rolled out the electronic order entry of chemotherapy order sets just within the past couple of weeks. So, we’re feeling the growing pains of such things right now, and we’ve been trying to proactively delineate those regimens where it hits most. And, obviously, carboplatin/paclitaxel is everywhere, so that’s going to be a big one. But, I think we need to prioritize and really look at those order sets, and proactively change out and add in the NK1 receptor antagonists where appropriate.

Howard Levine, PharmD: Practices differ for their EMRs. EMRs differ on how they handle these things, and most practices let the EMR feed them the information. So, you’re dependent upon the EMR provider to update the information. If you are, you have to ask them where they are, and typically there are priorities within their company and you are at their beholden. That being said, other practices take it in their own hands, and can manage and revamp their own treatment regimens. We do this when things come and change. It’s up to us. We don’t wait for our provider to say, “We’ve updated it for you.” We’ve updated it. New drugs come out and we build the regimens, immediately, because our prescribers like to use it before it’s available on the market sometimes. We have to build these kinds of things, so it’s really incumbent upon the practice to ask the question, “Have you updated this?” Or, they have to do it themselves.

Dawn Dolan, PharmD, BCOP: But it can be very difficult. We’re looking at 700 to 800 different order sets, and you have to weed through in which ones it’s appropriate to change, and in which ones it’s not. So, it’s almost becoming a job in and of itself in updating electronic order sets.

Howard Levine, PharmD: For one of our staff members, it is their job to update the EMR—one full-time job.

Beth Eaby-Sandy, CRNP, OCN: You’re exactly right.

Dawn Dolan, PharmD, BCOP: But, they need somebody like us to tell them what to do.

Beth Eaby-Sandy, CRNP, OCN: Right. When we did our last update, which was years ago when we added palonosetron to the highly emetogenic regimens, we had to have someone from the EMR company come and do all of them. So, this would be a huge undertaking, and this won’t be as easy as just searching the word “carboplatin.” Because in lung cancer, we have several regimens that are AUC of 2, so those wouldn’t fall into that. You’d have to really tease out which are the higher doses of carboplatin and add that. And that, again, would be someone hired to update those for us. It’s not been updated in ours yet, obviously. It would be a major overhaul.

Lee S. Schwartzberg, MD: It’s worth pointing out that this change occurred, this year, in the NCCN guidelines. In the MASCC/ESMO guidelines, last year, it was also reclassified as highly emetogenic, and we’re all in varying phases of implementing this. We have a care plan committee that does the same thing—it has to sort through every single order set and make the changes. And we’ve done that as well over the last couple of months.