Safety and Efficacy of Treatment Options for CINV

2020-02-14 19:00:00
Tags: safety,efficacy,CINV,formulation,doses,HSE




Experts in the management of chemotherapy-induced nausea and vomiting review the efficacy and safety of the available treatment options based on their mechanism of action.

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Katherine Lin, PharmD, BCOP: Touching base on the serotonin receptor antagonist, which we reviewed before. You have some first-generation agents. You have ondansetron, granisetron, and dolasetron. It depends on which agent you want to choose and which things you would want to look at. We had mentioned this before. All the agents are equally efficacious for first-generation when using them at appropriate doses.

There are some class effects that are similar and adverse effects that are across the board. All these agents cause headache, constipation. The thing that differs a little is the propensity to cause the QTc [corrected QT interval] prolongation. We know that it depends a little on the agent. It also depends on the dose and the formulation. As you increase the dose, you’re at higher risk for QTc prolongation. And we think the IV [intravenous] form is at higher risk of QTc prolongation than the PO [by oral route]. What really sets these agents apart is something you had already alluded to: its half-life and its formulation that it comes in. If you have a patient who’s having tons of nausea and vomiting and they don’t want to take anything by mouth, you have to go IV or you could potentially go with the subcutaneous extended-release forms, or something that’s an ODT [oral disintegrating tablet]. Ondansetron has an ODT. There’s also a transdermal patch with the granisetron. The main difference I see is the potential for QTc prolongation with obviously the highest potential to the dolasetron. That’s actually why they got rid of the IV formulation for that and then with the ondansetron and with the granisetron.

We also have a second-generation 5-HT3 receptor antagonist, as you had talked about, palonosetron. And the interesting thing about this drug is it has a much higher, 100-fold higher, binding affinity to the serotonin receptor than the other first-generation drugs. Also, with this 1, it has a longer half-life. The half-life, we think, is about 40 hours. It’s given IV. Arguably, it’s given once, although I suppose you can argue that you could repeat that for certain situations, but a half-life of 40 hours. Nonetheless, you do not see the QTc prolongation warnings with palonosetron as you do with the other drugs.

In theory, we think this 1 may actually be better. I know we had talked about pathophysiology before and we had said that the 5-HT3 receptor antagonists really have a role in preventing acute CINV [chemotherapy-induced nausea and vomiting] and not so much the delayed form. But this drug is actually very interesting in that it has some cross-talk with the neurokinin-1 receptor antagonist. We think by disrupting the cross-talk between 5-HT3 and neurokinin-1 that indirectly palonosetron can also inhibit the substance-P, so that’s why you might see some advantages using this agent with the delayed nausea and vomiting.

Bhavesh Shah, RPh, BCOP: I think it’s interesting. A lot of providers get confused because you can use 1 for delayed and then the other you can’t.

Katherine Lin, PharmD, BCOP: Yes.

Bhavesh Shah, RPh, BCOP: To this day I’ll be walking by the triage nurse’s desk, and I’ll identify a patient that’s calling in with delayed nausea and vomiting, and the patient received palonosetron and the provider is basically saying give them a prescription for Zofran. It’s still amazing. I think there is still some education that we need to do, that there are certain subtle differences among these 5-HT3s. If you go back into history, as long as I’ve been practicing, what I’ve seen is that we used to give continuous infusion of 5-HT3s because we thought that they would be better. We found out that actually that was equivalent to giving somebody an oral dose of 5-HT3. It’s interesting that now we have formulations that actually can have different impact on different receptors besides 5-HT3. That is how actually you have this benefit in patients for delayed emesis.

Katherine Lin, PharmD, BCOP: Then if you look at the neurokinin receptor antagonists as well, it’s kind of the same story. The thought is that you have several different agents. You have aprepitant, fosaprepitant. You have oral NK-1 receptor antagonists, rolapitant. And what the main difference is here is kind of the administration. Is it an oral form? Is it an IV form? And then the half-life and how long the drug acts. So there are advantages in giving an oral versus an IV. We have talked about this before. It depends on what the patient is appropriate for. If you have a patient who maybe has some cognitive deficits, maybe a patient with Parkinson disease or a patient with dementia, then maybe you would want to consider reducing their pill burden, so you give them something maybe IV in the clinic. Sometimes the insurance companies, the coverage providers make your decision for you. Usually the IV forms are covered by the medical benefit and your PO forms are covered by your pharmacy benefit. So sometimes the insurance companies steer you 1 way or another, but you should always take a look at your patient population. All are equally efficacious when given at an appropriate schedule. It’s really just looking at your patient population and seeing which agent they’re best suited for, IV or PO.

Bhavesh Shah, RPh, BCOP: Absolutely. Some of the things that I learned about NK-1 antagonists was obviously rolapitant actually has probably the longest half-life of any of them. Of course, the recommendation is not to give it more than 2 weeks. It has to have an interval of at least 2 weeks before you give a subsequent dose.