Nausea and Vomiting (PDQ®): Supportive care - Health Professional Information [NCI] - Prevention of Acute / Delayed Nausea and Vomiting (Emesis)
Palonosetron is a 5-HT3 receptor antagonist (second generation) that has antiemetic activity at both central and GI sites. In comparison to the older 5-HT3 receptor antagonists, it has a higher binding affinity to the 5-HT3 receptors, a higher potency, a significantly longer half-life (approximately 40 hours, four to five times longer than that of dolasetron, granisetron, or ondansetron), and an excellent safety profile.[Level of evidence: I] A dose-finding study demonstrated that the effective dose was 0.25 mg or higher. In two large studies of patients receiving moderately emetogenic chemotherapy, CR (no emesis, no rescue) was significantly improved in the acute and the delayed period for patients who received 0.25 mg of palonosetron alone compared with either ondansetron or dolasetron alone.;[Level of evidence: I] Dexamethasone was not given with the 5-HT3 receptor antagonists in these studies, and it is not yet known whether the differences in CR would persist if dexamethasone was used. In another study,[Level of evidence: I] 650 patients receiving highly emetogenic chemotherapy (cisplatin ≥60 mg/m2) also received either dexamethasone and one of two doses of palonosetron (0.25 mg or 0.75 mg) or dexamethasone and ondansetron (32 mg). Single-dose palonosetron was as effective as ondansetron in preventing acute CINV with dexamethasone pretreatment; it was significantly more effective than ondansetron throughout the 5-day postchemotherapy period. In an analysis of the patients in the above studies who received repeated cycles of chemotherapy, one author  reported that the CR rates for both acute and delayed CINV were maintained with single IV doses of palonosetron without concomitant corticosteroids. These data will require further review.
On the basis of the studies described above, palonosetron was approved by the FDA in July 2003 for the prevention of acute N&V associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy and for the prevention of delayed N&V associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. One randomized, double-blind, phase III trial compared palonosetron plus dexamethasone with granisetron plus dexamethasone for the prevention of CINV in patients receiving highly emetogenic chemotherapy. Palonosetron was equivalent to granisetron in the acute phase (first 24 hours) and better than granisetron in the delayed phase (24–120 hours), with a comparable safety profile for the two treatments.[Level of evidence: I] An open-label study was completed in a cohort of patients who had participated in this phase III randomized controlled trial comparing palonosetron to granisetron, with those who initially responded to palonosetron continuing the treatment over repeated cycles of chemotherapy. The investigators reported a good safety profile over time but provided limited data about adverse events. Another limitation of the study was that no more than 25% of patients were receiving palonosetron by cycle 4; the reasons for these withdrawals—whether lack of effect, adverse events, or other issues—were not reported.