Update on the management of chemotherapy-induced nausea and vomiting – focus on palonosetron

Abstract

PurposeNausea and vomiting are major adverse effects of chemotherapy and can greatly impact patients’ quality of life. Although chemotherapy-induced nausea and vomiting (CINV) prevalence is high, treatment remains difficult. Palonosetron is a 5-hydroxytryptamine receptor antagonist (5-HT3RA) approved for treatment of CINV. The purpose of this review is to discuss existing and emerging therapeutic options, and examine studies focusing on palonosetron with regards to efficacy, pharmacology, tolerability, safety, and patient-derived outcomes.MethodsA literature search was conducted using Ovid MEDLINE and EMBASE to identify relevant studies using palonosetron alone or in combination with other antiemetics. Studies were extracted if they included complete response (CR), complete control (CC), no nausea, no vomiting, and no rescue medications as an endpoint. Studies were also included if safety endpoints were examined.ResultsPalonosetron alone has been shown to improve CR and CC rates for patients receiving low, moderate, or high emetogenic chemotherapy. Rates were further improved with the addition of dexamethasone, a corticosteroid. Furthermore, the addition of neurokinin-1 receptor antagonists, such as netupitant markedly improved efficacy profiles compared to palonosetron alone. Aprepitant is an antiemetic that has exhibited positive results in combination with palonosetron. Recently, a new drug consisting of netupitant and palonosetron (NEPA) has demonstrated significantly more efficacious prevention of CINV. Regardless of the combination, palonosetron has been well tolerated. The most common adverse events were constipation, headache, fatigue, and dizziness, with the majority of patients describing them as only mild or moderate.ConclusionPalonosetron, alone or with other antiemetics, has improved CINV treatment due to its ability to significantly reduce delayed phases of CINV, compared to similar 5-HT3RAs. Palonosetron is both more effective than first generation 5-HT3RAs and safer, as it results in a smaller prolongation of the QTc interval, compared to other 5-HT3RAs.

The Effect of a Combination Treatment Using Palonosetron, Promethazine, and Dexamethasone on the Prophylaxis of Postoperative Nausea and Vomiting and QTc Interval Duration in Patients Undergoing Craniotomy under General Anesthesia: A Pilot Study

“…To begin with, this study enrolled 40 subjects who received study medication and completed all the assessments, but the study was designed without a control group; therefore, we were not able to compare the results from this regimen. In addition, headache, constipation, fatigue, and dizziness are the most common side effects of palonosetron; however, both side effects are also expected postoperative symptoms after craniotomies ( 18 ).…”

“…Palonosetron is the latest serotonin receptor antagonist ( 3 , 6 – 8 , 13 , 16 , 17 ). Serotonin is an ubiquitous central and peripheral neurotransmitter thought to be the predominant mediator of the perception of nausea and triggering of the vomiting response ( 18 ). This occurs in both the brain and the periphery via the serotonin 5-hydroxytryptamine type 3 [5-HT(3)] receptor pathways ( 19 ).…”

“…The most effective dose for PONV is a single 0.075 mg IV dose administered over 10 s right before anesthesia induction ( 5 , 6 , 12 , 13 ). The most common side effects of palonosetron described in the literature are electrocardiogram QT prolongation, bradycardia, headache, and constipation ( 18 , 20 ). The US Food and Drug Administration (FDA) approved its use for prevention of PONV in March 2008 ( 7 , 20 ).…”

Newest Drugs for Chronic Unexplained Nausea and Vomiting

“…Likely because of these actions on NK 1 receptors, palonosetron reduces delayed nausea and vomiting after chemotherapy whereas older 5-HT 3 antagonists only are effective during the acute phase of CINV. In a recent review of phase 3 and 4 trials, palonosetron produced complete responses ranging from 57% to 84% for acute CINV and 54% to 94% for delayed CINV (25). One meta-analysis reported a favorable safety profile for palonosetron with lesser prolongation of the electrocardiographic QTc interval compared to other 5-HT 3 antagonists (26).…”

Management of acute and delayed chemotherapy-induced nausea and vomiting: role of netupitant–palonosetron combination

“…In the past 2 decades, there has been substantial progress in the control of CINV related to the introduction of effective antiemetic agents, including the first- and second-generation serotonin (5-hydroxytryptamine [5HT]) type 3 receptor antagonists (5HT 3 RAs; eg, ondansetron, granisetron, and palonosetron) and neurokinin-1 receptor antagonists (NK1RAs, eg, aprepitant, fosaprepitant, casopitant, and rolapitant). 4 An important benefit of the newer antiemetic agents appears to be associated with their prolonged pharmacological effect and consequently improved ability to control the delayed CINV, which can develop even several days after chemotherapy administration. In addition to pharmacotherapy, patient education regarding the timing, prevention, and treatment of CINV is another key component of successful management of CINV.…”