Various Treatments and Doses Used for Prophylaxis of CINV

Bhavesh Shah, RPh, BCOP, and Katharine Lin, PharmD, BCOP, discuss the various treatment options, mechanism of action and dosing of agents used for chemotherapy-induced nausea and vomiting.

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Bhavesh Shah, RPh, BCOP: I’d also like to point out that we’ve never actually used palonosetron in our institution. Believe it or not, we’ve always been olanzapine users. Our journey started at least 6 or 7 years ago, when Rudolph M. Navari actually had presented the results in which he compared—in highly emetogenic chemotherapy regimen—olanzapine versus NK-1 receptor antagonists and cisplatin regimen. It was about a 100-patient trial, and it was pretty significant. At that time is when Emend [arepitant] was first approved, or it was the only brand NK-1 that was out there.

We were early adopters of olanzapine and had a significant experience with it in practice because we were having such cost barriers with a lot of patients. A lot of our providers were using olanzapine as an alternative but actually saw a similar benefit.

We did a retrospective analysis in our analysis in terms of utilization of highly emetogenic chemotherapy regimen with Emend versus with olanzapine, and we noticed that there was actually a lower number of CINV [chemotherapy-induced nausea and vomiting]—related missions in our patient population, which actually confirmed a lot of our provider’s practice. We’ve always been using that. Believe it or not, there are other properties that olanzapine has that may help patients sleep better. There have been studies with appetite stimulation. I don’t think that’s really fully panned out, but there are always other benefits that olanzapine has. I’m always an olanzapine guy. But it is interesting because when you try to start a patient on olanzapine, there are concerns like, “Hey, why are you starting me on antipsychotics,” right?

Katherine Lin, PharmD, BCOP: Yeah, yeah.

Bhavesh Shah, RPh, BCOP: There’s definitely some education that we have to do for our patients. But I love the fact that others also have great nausea control in the delayed emesis. This is why I think it was added to the guidelines. You have almost a 50% lower nausea in the delayed phase, versus NK-1 receptor antagonists. I think that truly makes it powerful. I was fortunate to be a co-investor on the randomized phase III control trial for olanzapine for that specific study, so that was very powerful. If there are other drugs that you actually wanted to talk about, we’d love to hear your opinion about the NK-1 receptor antagonists. I’m sure you have multiple ones now there too.

Katherine Lin, PharmD, BCOP: I have a question for you. Do you have all your high-risk patients? Do you start them all on an olanzapine backbone, or are there certain patients you select out of that and say that these are going to be good candidates for olanzapine regimens?

Bhavesh Shah, RPh, BCOP: That’s a great question. We actually do olanzapine for all patients because of the results that we’ve had. I think the NK-1 receptor antagonist is basically optional for a lot of those patients.

Katherine Lin, PharmD, BCOP: That’s really interesting.

Bhavesh Shah, RPh, BCOP: Yes.

Katherine Lin, PharmD, BCOP: I can tell you that my practice has been that I don’t necessarily start everybody off, even if they’re highly emetogenic risk. Not all comers would I consider necessarily for olanzapine. My practice has been more so that we do a 5-HT3 backbone. We have been big users of palonosetron and with the corticosteroid, plus the NK-1. And then if patients are the highest of the high risk. And where I start to think of those patients is the cisplatin patients. And not only cisplatin patients; it’s the multiday cisplatin patients. For those patients I definitely would consider giving prophylactic olanzapine. And I’ll be honest with you. I think there’s risk versus benefit on whether you want to start them. Because if they have breakthrough on the regimen that I’m on, you know we’re going to have to look into some drugs that I wouldn’t necessarily use first line.

But if you get better control and you don’t experience that breakthrough, I think that would be an argument to use olanzapine. But in my practice, I specifically tend to use a triplet therapy. If patients have breakthrough on that, the first agent I’m going to is olanzapine, especially if it’s the nausea component. Because as you mentioned, it’s been so highly effective in the delayed nausea. And then for patients who are the highest of the high risk, I definitely agree with you that those patients really benefit from prophylaxis olanzapine.

Bhavesh Shah, RPh, BCOP: Do you use 5 mg or 10 mg in your practice?

Katherine Lin, PharmD, BCOP: That’s a great question. The data have all been shown to be with the 10 mg. Although I believe there was a study out recently that showed that you could probably get away with 5 mg. It depends on the patient. We talked about individualizing a lot. If I have a younger patient who doesn’t have any other sedating medications—no other medications that I’m really concerned about QTc [corrected QT interval] prolongation with—I typically start them at 10 mg, because if they’re appropriate I do want them to receive the full benefit from the medication. If I have an older, frailer patient—with some cognitive deficit to begin with, who may be on some other medications that can cause somnolence—I tend to go lower. Then I’ll start at 5 mg. I actually have had some patients with concern when we’ve done 2.5 mg, and we’ve seen even added benefit from that.

Bhavesh Shah, RPh, BCOP: One of the things we didn’t talk about are some of the recent updates that have been with 5-HT3 dosing with ondansetron where it’s the lower, about 32-mg dose was reduced to a maximum of 16 mg. Is that correct, because the QTc prolongation? Definitely. One of the 5-HT3s is no longer used, probably dolasetron, which also has some cardiac issues, which is why we don’t see that usually being used too often in the current environment.