title: Update on the management of chemotherapy-induced nausea and vomiting - focus on palonosetron.
abstract: OBJECTIVE
  Nausea 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Palonosetron 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.
  
  
  CONCLUSIONS
  Palonosetron, 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.
authors.affiliation: Department of Pharmacy, Odette Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Odette Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Marko
authors.initials: M
authors.lastname: Popovic
authors.affiliation: Department of Pharmacy, Odette Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Pasetka
authors.affiliation: Department of Pharmacy, Odette Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Natalie
authors.initials: N
authors.lastname: Pulenzas
authors.affiliation: Department of Pharmacy, Odette Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Soha
authors.initials: S
authors.lastname: Ahrari
authors.affiliation: Department of Pharmacy, Odette Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Chow
authors.affiliation: Department of Pharmacy, Odette Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Carlo
authors.initials: C
authors.lastname: DeAngelis
keywords: chemotherapy-induced nausea and vomiting; efficacy; palonosetron; patient-reported outcomes; pharmacology; safety