Palonosetron in the prevention of chemotherapy-induced nausea and vomiting: an evidence-based review of safety, efficacy, and place in therapy

Abstract

Introduction: The second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist palonosetron is effective in the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly and moderately emetogenic chemotherapy (HEC and MEC, respectively). In addition, palonosetron has been the first and, at present, the only 5-HT3 receptor antagonist to have a specific indication for the prevention of delayed CINV associated with MEC. The unique pharmacology of this antagonist is thought to partly explain its improved efficacy against delayed symptoms.Aims: To review the evidence underlying the use of palonosetron in preventing CINV.Evidence review: A recent meta-analysis consistently showed that palonosetron significantly increases the control of both emesis and nausea during the acute and delayed phases after single-day HEC or MEC. Consistent with these findings from trials that did not include an neurokinin-1 (NK-1) receptor antagonist, randomized controlled trials recently showed that a triple combination with palonosetron achieves significantly better control of delayed CINV, particularly delayed nausea, in patients undergoing HEC or the high-risk combination of an anthracycline and cyclophosphamide (AC). Evidence from randomized studies also supports palonosetron as a valuable option to reduce the total corticosteroid dose administered in patients undergoing multiple cycles of MEC or AC chemotherapy. Additional benefits of palonosetron include the lack of a warning on cardiac safety and no known clinically significant drug–drug interactions.Place in therapy and conclusion: Evidence currently available indicates that palonosetron significantly adds to the clinician’s ability to effectively control CINV in patients undergoing HEC or MEC. It is recommended in the international guidelines for the prevention of CINV caused by MEC. The high safety profile and the opportunity to reduce the total corticosteroid dose with no loss in efficacy against delayed CINV should also contribute to a wider use of palonosetron in clinical practice.

One-Day Versus Three-Day Dexamethasone in Combination with Palonosetron for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Individual Patient Data-Based Meta-Analysis

“…Therefore, dexamethasone dose could be reduced irrespective of whether the patient is younger or older than 60 years. In addition to the risk factors discussed above (emetogenic potential of chemotherapy, sex, age, and alcohol consumption habit), other known risk factors should be noted, including rapid 5‐HT 3 receptor antagonist metabolism, 5‐HT 3 receptor polymorphism, history of motion sickness, anxiety, and fatigue . We acknowledge that these other risk factors were not taken into consideration in the present study.…”

“…However, it should be noted that the 5‐HT 3 receptor antagonists included were of an older generation than palonosetron because their meta‐analysis was conducted in 2000, before palonosetron was approved in 2003. Celio et al conducted a narrative review of the evidence about the efficacy and safety of palonosetron, but they did not examine the necessity for concomitant dexamethasone. The present study is the first to assess the clinical relevance of the dexamethasone‐sparing strategy in a systematic review with IPD meta‐analysis.…”

“…Palonosetron, a second‐generation 5‐HT 3 receptor antagonist, is superior to the first‐generation antagonists in efficacy and safety, having greater binding affinity for the 5‐HT 3 receptor and a longer elimination half‐life . Additionally, palonosetron is the only agent in the class that is approved for the prevention of delayed CINV after MEC . Dexamethasone synergistically enhances the antiemetic efficacy of 5‐HT 3 receptor antagonists .…”

Palonosetron compared with ondansetron in pediatric cancer patients: multicycle analysis of a randomized Phase III study

“…Nervous system disorders (headache, dizziness and dyskinesia) were the most commonly reported adverse events related to treatment. Older class 5-HT 3 receptor antagonists are reportedly associated with a risk of inducing adverse cardiac events (electrocardiogram changes and arrhythmias), although studies suggest palonosetron to be less of a risk for these events [10,28,29]. In total, treatment-related cardiac disorders were reported in one patient receiving 10 μg/kg palonosetron and two receiving ondansetron.…”

“…Palonosetron hydrochloride (Aloxi ® ) is a comparatively new 5-HT 3 receptor antagonist with a higher affinity (at least 30-fold higher) for the 5-HT 3 receptor, and a longer plasma elimination half life compared with older class agents (ondansetron, granisetron and dolasetron) [10]. Its unique interaction with the 5-HT 3 receptor at the molecular level, and its effects on the NK 1 signaling pathway may offer an advantage for efficacy over older agents in this class [11][12][13].…”