Granisetron has demonstrated efficacy in preventing and controlling N&V at a broad range of doses (e.g., 10–80 µg/kg and empirically, 3 mg/dose). In the United States, granisetron injection, transdermal patch, and oral tablets are approved for initial and repeat prophylaxis for patients receiving emetogenic chemotherapy, including high-dose cisplatin. Granisetron is pharmacologically and pharmacokinetically distinct from ondansetron; however, clinically it appears equally efficacious and equally safe.[32,33,34,35][Level of evidence: I] Both granisetron formulations are given before chemotherapy, as either a single IV dose of 10 µg/kg (0.01 mg/kg) or 1 mg orally every 12 hours.
Both granisetron formulations and ondansetron injection share the same indication against highly emetogenic chemotherapy. In contrast, the oral ondansetron formulation has been approved only for use against N&V associated with moderately emetogenic chemotherapy.
Currently, granisetron injection is approved for use without dosage modification in patients older than 2 years, including elderly patients and patients with hepatic and renal insufficiency. Oral granisetron has not yet been approved for use in pediatric patients.
Both oral and injection formulations of dolasetron are indicated for the prevention of N&V associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses. Oral dolasetron should be dosed as 100 mg within 1 hour before chemotherapy. Dolasetron should be given IV or orally at 1.8 mg/kg as a single dose approximately 30 minutes before chemotherapy.
The effectiveness of oral dolasetron in the prevention of chemotherapy-induced nausea and vomiting (CINV) has been proven in a large randomized, double-blind, comparative trial of 399 patients.[Level of evidence: I] Oral dolasetron was administered in the range of 25 to 200 mg 1 hour prior to chemotherapy. The other study arm consisted of oral ondansetron (8 mg) administered 1.5 hours before chemotherapy and every 8 hours after chemotherapy for a total of three doses. Complete response (CR) rates improved with increasing doses of dolasetron. Both dolasetron 200 mg and ondansetron had significantly higher CR rates as compared with dolasetron 25 or 50 mg. (CR was defined as no emetic episodes and no use of escape antiemetic medications.) Dolasetron injection has also been proven effective in the prevention of CINV.[Level of evidence: I]
Palonosetron is a 5-HT3 receptor antagonist (second generation) that has antiemetic activity at both central and gastrointestinal 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.