CINV: The Role of NK1 Receptor Antagonists


Transcript:Lee S. Schwartzberg, MD: That’s a great segue into when we talk about interactions about the second class of drugs and the newer drugs in particular, the NK1 antagonists. And, Eric talked about NK1s. You want to just talk a little bit about the development of those classes?

Eric Roeland, MD: The most common drugs that we have in the United States are aprepitant and fosaprepitant. And, I think Charles has some great knowledge on both of them. The aprepitant is primarily oral and fosaprepitant is IV. And, I think, based on where you are and your institution, you either use aprepitant or fosaprepitant.

James Natale, PharmD, BCOP: That’s correct.

Lee S. Schwartzberg, MD: So, Charles, you did some of that work?

Charles L. Loprinzi, MD: Well, I actually didn’t do any of the work, but I’ve been around for a while, so I was around during the work. But, aprepitant was the first one that came about. It’s an oral one. And initial studies looked at it with a 5-HT3 receptor antagonist or without a 5-HT3 antagonist. If you give it alone in the acute setting, you get a lot more nausea and vomiting; 50% of the people were vomiting with the NK1 receptor, aprepitant, alone, if they didn’t get on ondansetron at that time, or granisetron, versus 80% were not vomiting if they got the granisetron. In the acute setting, the 5-HT3 receptor antagonist is better. But, then, in the chronic setting, or the delayed setting, the aprepitant was better than the granisetron. If you add them both together, you get even more benefit from them.

So, that was a 3-day regimen. Then came fosaprepitant, and fosaprepitant is just the IV formulation, if you will, of the same cytotoxic drug. You give it intravenously only on day 1. Going back beyond that, aprepitant was a 3-day regimen. Some people couldn’t afford the other 2 days. You’d probably get a lot of your benefit with just the 1-day dose, although that hasn’t been proven and shown.

Fosaprepitant came in, and Steve Grunberg did the trial looking at 1-day fosaprepitant versus the 3-day aprepitant. Patients did equally well, and there was little in the way of side effects and all. It was only for one dose. And most patients got cisplatinum in that particular trial. We changed practice at our shop. And the way we change practice, it’s automatic. Everybody gets this unless the doctor changes it, and we changed everything from aprepitant to fosaprepitant. Then, the nurses there said, “Hey, wait a second, we’re getting a lot of venous toxicity, especially with Adriamycin-based regimens.”

Now, at Mayo Clinic, we don’t use central catheters all that often. That happens in probably 20% of my patients, whereas other practices it’s more like 90% or 100%. We don’t see the oncologist for chemotherapy until they get that. But, for peripheral, we got up to 50% of terrible venous toxicity from it. And others over in Japan reported the same thing that we did. So, we switched back to the oral aprepitant, if people had peripheral IVs. It was a matter of central IVs, so it wasn’t a particular problem there.

And, again, it wasn’t seen with Grunberg, but it was seen a little bit more as 3% versus 1% in the paper. But, in our paper, it was like 40% when you got multiple doses of Adriamycin therapy. So, those were the things that came around. And, then, there are newer drugs that have come about, which we’ll probably talk about in a bit.

Eric Roeland, MD: Jim, I don’t know if you’ve done this, but at least at our institution for the fosaprepitant, if they do have that bad experience, we just put it in a larger volume.

Lee S. Schwartzberg, MD: I think many practices do, now, as compared to the label dosing, if you want to talk about that.

James Natale, PharmD, BCOP: We do do that. We will put in a larger volume. Although most of our patients will have central catheters, we do use the ones they’re dosing upfront. So, we haven’t had a major problem with that.

Eric Roeland, MD: Those that do, we’ll put in larger volume.

Charles L. Loprinzi, MD: We did subsequently look at the cisplatin-based therapies as opposed to the AC (anthracycline/cyclophosphamide) with peripheral IV. And about 15%, 20% of them have a problem as opposed to 40%. So, it’s less of it. And, later on, it’s after multiple doses of it, as opposed to after the first, second, or third dose of the Adriamycin.

Lee S. Schwartzberg, MD: So, cumulative irritant of peripheral veins, basically.

Charles L. Loprinzi, MD: But, if you have a central vein, then you’re okay.

Lee S. Schwartzberg, MD: Are you giving oral aprepitant all on day 1, or are you still using the Tri-Pack?

Charles L. Loprinzi, MD: The 3-day, but sometimes, financially, they can get day 1 at the clinical and they can’t get the other two. You say, “You’re probably going to do alright with it.”

Lee S. Schwartzberg, MD: That was my experience, too, and so they often didn’t fill the prescription for day 2 and 3.

Charles L. Loprinzi, MD: And if they did fine, they did fine. If they didn’t, if they had a bad experience, then the next time you up them, maybe give them day 2 and day 3.

Lee S. Schwartzberg, MD: Yes, it’s interesting. We’re on the side where 90% to 100% of our patients have portacaths, particularly for AC-based therapy, because we’re afraid of that. So, we don’t see that then. We use fosaprepitant.

Transcript Edited for Clarity

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