Palonosetron Hydrochloride in the Treatment of Chemotherapy-Induced Nausea and Vomiting

Abstract

Chemotherapy-induced nausea and vomiting (CINV) is among the most unpleasant and stressful aspects of chemotherapy. Poorly controlled nausea and vomiting may have negative impacts on clinical treatment and quality of life. Clinical trials aimed at the prevention of CINV have focused on both acute and delayed phases of CINV. The use of first generation serotonin subtype 3 serotonin (5-HT3) receptor antagonists has significantly improved symptom control in acute CINV. However, they are less effective in controlling delayed CINV Palonosetron is a second generation 5-HT3 receptor antagonist with high potency, selectivity, prolonged half-life, and a unique allosteric binding mechanism. Previous trials which compared palonosetron to other first generation 5-HT3 antagonists had used the prevention of delayed CINV as a secondary end point. Recent data have demonstrated palonosetron, when used with a corticosteroid, was superior to granisetron in the prevention of delayed CINV as a primary end point. This article will review recently published literature focusing on mechanism of action, metabolism, pharmacokinetics, clinical efficacy, and safety of palonosetron in the treatment of CINV, specifically delayed CINV.

A Systematic Review and Meta-Analysis of Intravenous Palonosetron in the Prevention of Chemotherapy-Induced Nausea and Vomiting in Adults

“…However, acute and delayed CINV might have overlapped. CR rate in the overall phase was probably a more useful endpoint [37].…”

Pilot study on the efficacy of an ondansetron- versus palonosetron-containing antiemetic regimen prior to highly emetogenic chemotherapy

“…Nausea and vomiting can adversely affect patients' quality of life, cause electrolyte imbalances and dehydration, increase healthcare costs (increased medication use, hospital admissions, and longer hospital stays), and could lead to delays in treatment or patient refusal of further treatment [1, 2]. …”

“…Palonosetron differs from first-generation 5HT3 antagonists [2, 6]. It has a longer half-life (around 40 h compared with 3–9 h with other 5HT3 antagonists) and a 100-fold greater binding affinity to the 5HT3 receptor [7–10].…”

“…Due to its unique pharmacokinetic parameters, a single dose of palonosetron provides protection against delayed CINV, unlike the currently available 5HT3 antagonists. Palonosetron is FDA-approved for the prevention of acute and delayed CINV associated with moderately emetogenic chemotherapy and acute CINV associated with HEC [2, 6]. …”