Transcript:Lee S. Schwartzberg, MD: Let’s talk about the pathophysiology of CINV. We’ve learned a lot about this over the last couple of decades, which has driven the advances in the drugs we have. Eric, can you tell us a little bit about this?
Eric Roeland, MD: Nausea and vomiting, it turns out, is pretty complex and is an important phenomenon because back in the day, you wanted to avoid bad stimuli that caused nausea and vomiting. But in the setting of chemotherapy-induced nausea and vomiting, we really think about two neurotransmitters in particular—serotonin and substance-P, or neurokinin-1. It’s much more complicated than that, and we think about steroids, cannabinoids, benzodiazepines, and GABA receptors. In the same way that we focus on the receptors in which we have tools and oncology, we also do that in nausea and vomiting. So, when we talk about serotonin in particular, we’re usually talking about the gut, although there’s some overlap with some of these neurotransmitters.
I like to simplify it and think about serotonin mostly in the gut, and primarily the 5-HT3 receptors, which come from a cell called the enterochromaffin cell, which lines the gut. The drugs that we have that target those are the 5-HT3 receptor antagonists, which I’m sure we’ll talk about today. And then when we’re talking about the NK1 receptor antagonists, we’re thinking mostly about the brainstem and primarily the chemotherapy receptor trigger zone. And with that receptor, we have a whole new class of medications called the NK1-receptor antagonists that really help in the delayed phase of chemotherapy-induced nausea and vomiting.
Lee S. Schwartzberg, MD: There’s a feedback loop from the gut up to the brain, which then triggers the emesis reflex if the stimulus is high enough.
Eric Roeland, MD: Yes. To try to simplify things, we think of using the 5-HT3 receptor antagonist primarily in the acute setting, which is within the first 24 hours. And then we think of using the NK1 receptors in the delayed phase—although that’s pretty unofficial. But, in general, that’s a good way to think about it.
Lee S. Schwartzberg, MD: Great. So, not only do we know about the pathophysiology, but we’ve been able to clinically define the different types of CINV that we see. And there are differences based on the emetogenic drugs that we’ve been giving now for several decades. Jim, can you tell us a little about those different categories?
James Natale, PharmD, BCOP: Generally, when we talk about chemotherapy-induced nausea and vomiting, we are talking about four different categories. Although, as Eric had mentioned, there’s certainly some overlap. Acute nausea and vomiting, that’s generally defined as happening within the first 24 hours of chemotherapy. Delayed nausea and vomiting is generally 24 hours, up to about 120 hours. Breakthrough nausea and vomiting, which happens after what we consider effective prophylaxis. And then the anticipatory nausea and vomiting happens actually prior to the administration of chemotherapy.
We think it’s a conditioned response that we are born with, an innate need to get rid of toxic stimuli. And that’s usually brought on by taste, smells, sights. I had one patient that told me privately, “Please, don’t tell my physician that just looking at him brought back the scenario of nausea and vomiting with the first cycle of chemotherapy.” She had to get over that fear when she walked into the clinic. So, those are generally the definitions we use. That being said, most of those are based on older, single-day regimens. And as we get into more complex therapies in multi-day regimens, sometimes those definitions definitely blur.
Lee S. Schwartzberg, MD: And a lot of this is actually based on the original emetogenic drug cisplatin, which has sort of a biphasic emesis. So, the first few hours, sometimes right when you’re in the chair, and then a couple of days later.
James Natale, PharmD, BCOP: Yes.
Lee S. Schwartzberg, MD: But it’s fair to say that the clinical trials have focused on the 5 days up to that 120 hours. But there are definitely patients who have nausea and vomiting from chemotherapy that might last longer, as well.
Transcript Edited for Clarity