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

Abstract

Purpose

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.

Conclusion

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.

Keywords:

• chemotherapy-induced nausea and vomiting
• palonosetron
• efficacy
• safety
• pharmacology
• patient-reported outcomes

Acknowledgments

We thank the generous support of the Bratty Family Fund, Michael and Karyn Goldstein Cancer Research Fund, Pulenzas Cancer Research Fund, Joseph and Silvana Melara Cancer Research Fund, and Ofelia Cancer Research Fund.

Disclosure

The authors report no conflicts of interest in this work.