Understanding the Guidelines for Anti-Emetics in CINV

Transcript:Lee S. Schwartzberg, MD: I think we should back up for a moment and just say the goal of therapy is to prophylax patients and, ideally, that they wouldn’t have any nausea and vomiting. And we know we’re not quite there yet. We’ve made a lot of progress certainly in the acute, as you’ve all mentioned, and the majority of patients now don’t have acute nausea or vomiting. We still have problems with delayed, which we’ll talk about at some length. But let’s talk about the different guidelines that are out there and how they differ, how they’re alike. Charles, can you lead us off on that?

Charles L. Loprinzi, MD: I won’t finish, because there’s a lot to talk about there. It’ll get things started with these things. So, there are guidelines around. They’ve been around for quite some time. There are ASCO guidelines and MASCC/ESMO guidelines. Those are together now; they weren’t in the past. There are ONS guidelines and there are NCCN guidelines. And they have a lot of similarities. Basically, the idea is to try to prevent nausea and vomiting at a reasonable cost. If you say you want to prevent all nausea and vomiting, then you do minimally emetogenic chemotherapy to give the whole bunch. But that’s, again, very expensive, and we have to think about that aspect of things. So, the different chemotherapies are rated in terms of minimal, mild, moderate, and highly emetogenic chemotherapy.

For most of the highly emetogenic chemotherapy and NK1 receptor antagonists, say 5-HT3 receptor antagonists and dexamethasone, they are recommended by basically all of the guidelines there. If you get down to moderately emetogenic, then a 5-HT3 receptor antagonist—dexamethasone for sure, maybe not the NK1 receptor antagonist—and probably using the palonosetron version of the 5-HT3 receptor antagonist because of its prolonged half-life there are recommended. In that setting, if a person chooses to use an NK1 receptor antagonist, then a lot of the guidelines say, “Well, you don’t have to use the more expensive palonosetron because you have the NK1 receptor antagonist on board there.”

The one guideline that jumped the gun a little bit, if you will, was the NCCN guidelines. It added, a year or so ago, olanzapine to the mixture, and I think we might talk about that later. And while the other guidelines have not, they’re talking about it and they’re starting to, because that is a new player on the block.

Rebecca Clark-Snow, RN, BSN, OCN: So, if I could just interject a little bit about guidelines. Guidelines are wonderful, but they’re only good if they’re used. And they’re simply that, they’re guidelines. And each institution can incorporate the guidelines as it fits their particular institution. We’re hearing a lot about adherence these days, difficulty in physicians and practices actually following guidelines, and what do we do to help that or alleviate that. I think there are a few things that we can do that many institutions are already doing, and that’s to have standardized orders. Usually electronic medical records (EMRs) and past guidelines already incorporate it into each chemotherapeutic regimen, so there’s less of a chance to order the wrong thing, if you will. But, adherence, I think, is a major issue, and we’re really looking at that from lots of different angles.

Lee S. Schwartzberg, MD: That’s interesting. Go ahead.

Charles L. Loprinzi, MD: I think that’s right on, and I had a chance to review an old paper I was a participant in. It went back to when we first developed our antiemetic guidelines in 1995, so 20 years ago. The nurses figure out grade 1, 2, 3, 4 emetogenic chemotherapy, then we have what you give for each one of those, and it’s set up so when you order the chemotherapy, that comes up.

The doctor can change it, but it’s easier not to change it. You don’t have to remember which is a moderate emetogenic regimen, for example. We actually have 5 grades for very highly emetogenic. If you do poorly with your highly emetogenic in your next go-round, then you jump up to where we actually had the NK1 receptor antagonists and palonosetron in that particular setting for that oral if we’re giving cisplatinum and radiation, because that caused so much trouble.

We recently were able to look at that and say, “It seems like it should help with people using the guidelines.” We actually went and looked and found that 95% compliance is what we did. And in the few times where it wasn’t, it was because of a drug interaction, so it was good it wasn’t 100% compliance. But that is a way that you can, in fact, do that and make it happen. It’s a bit clumsy in ways, because what if you want to change this and that? It’s not easy, and you might not have the other drug on the formulary. And to get the whole institution to change things can go through a process; let’s double-check and ask the pharmacists and the nurses. But it does work quite nicely in that setting.

Lee S. Schwartzberg, MD: So, that’s the Mayo Clinic, and you’re the standard that we all aspire to. But we do know that in practice, despite the fact that almost everyone has a health record today, we don’t use the guidelines. And it’s curious to me that, particularly as it comes to supportive care, sometimes they’re not used, if they’re built in. If we don’t build them in, then we’re even further off guidelines. What’s been your experience?

James Natale, PharmD, BCOP: That’s been our experience, and certainly it’s been well published now that the adherence to guidelines isn’t great. But if you do adhere to the guidelines, outcomes are much better. We have leaned on technology and EMRs to build things in. And pharmacy was a big player, at least in our institution, along with medicine and nursing. So, we do build them in now and adherence rates have been much better.

Eric Roeland, MD: I think it also highlights the role of the pharmacist and the nurse, because the oncologists now, with all these new drugs, we get an e-mail each day about a new drug approved and just the amount that we’re all responsible for. So, I’m finding that pharmacists are really helping set these orders up so that it’s most efficient for physicians. And really for our trainees, when I have talks with my Fellows about highly emetogenic chemotherapy, I start off the talk with, what the heck is HEC? Because very few Fellows even know what the different categories are and how to approach them. And those days of writing out orders, actually knowing them, and learning them by writing them out are just gone.

Lee S. Schwartzberg, MD: So, there’s something to be gained. Certainly, there is standardization when the pharmacists do it. There’s also something to be lost, because you don’t remember and you are doing the initial ordering exactly by what’s in that whole very complex care plan that we have now. I want to go back because of this. I want our audience to be fully aware of the way that the guidelines are set up and the categories. They’re all divided into acute and delayed recommendations. Eric, you want to mention a little bit about those differences?

Eric Roeland, MD: I think acute, we decided it’s defined arbitrarily as less than 24 hours, and we’re stuck with that based on cisplatin. And then delayed is the 24-hour period up to about 5 days. Again, when we’re thinking about acute, the 5-HT3 receptor antagonists have a much larger role. And then with the delayed, it’s the NK1 receptor antagonist. I think that’s what you’re trying to get me at.

Lee S. Schwartzberg, MD: Right. Let’s talk about the use of Decadron, as well.

Eric Roeland, MD: Okay. We have emerging data, actually, so the common question for people when I talk about this is, “Dexamethasone, do I need to give it for the full 3 days in the delayed phase?” And even at ASCO this year, there’s a poster describing that day-1 dexamethasone might be enough. And any pharmacist when I talk to them about this, they laugh, because we all know the biologic half-life of dexamethasone is 36 hours because it’s fluorinated. Yet, history has been that we’ve included it, and it could be that we’re just finally at a point in history where we have such good tools with the 5-HT3 receptor antagonist and NK1 that we can start to say, “Hey, do we need to give dexamethasone and give our patients all these side effects for those days?”

Lee S. Schwartzberg, MD: In a breast cancer practice, but particularly where we give a lot of dose-dense chemotherapy, if we have to give 3 days of dexamethasone every 14 days, that’s a lot of corticosteroids. And the women don’t like it. They have lots of issues, as all people do with getting hyper and diabetes flaring. What’s been your experience?

Charles L. Loprinzi, MD: I agree with you. There’s this ASCO abstract this afternoon that’s supposed to be presented, and there are other papers that have come out recently that suggest that you can get by with just day-1 dexamethasone. And my own philosophy, give them 3 days of it. If you have no nausea and vomiting on day 1, then you’re probably going to do fine. If you have nausea and vomiting, then probably take day 2 and 3. That is how I’ve come down on that.

Transcript Edited for Clarity