Palonosetron safe, effective in preventing chemotherapy-induced nausea, vomiting

Palonosetron plus dexamethasone was superior to granisetron plus dexamethasone in preventing chemotherapy-induced nausea and vomiting in delayed phase, according to data from a phase-3 trial. The combination proved non-inferior to granisetron in the acute phase.

Researchers conducted a randomized, double blind, double-dummy trial comparing the second-generation 5HT3-receptor antagonist, 0.75 mg palonosetron (Aloxi, Helsinn Healthcare) plus 16 mg dexamethasone with 40 mcg/kg of the first-generation agent granisetron plus 16 mg dexamethasone for the prevention of chemotherapy-induced nausea and vomiting. Primary endpoints were complete responses in acute (zero to 24 hours after therapy) and delayed (24 to 120 hours after therapy) phases.

The trial included 1,114 patients with cancer receiving emetogenic chemotherapy. During the acute phase, 418 of 555 patients (75.3%) in the palonosetron group achieved a complete response compared with 410 of 559 patients (73.3%) in the granisetron group (mean difference=2.9%; 95% CI, 2.70-7.27). During the delayed phase, complete responses occurred in more patients in the palonosetron group compared with the granisetron group (56.8% vs. 44.5%; P<.0001).

Constipation and raised concentrations of serum aminotransferases were among the most commonly reported adverse events; no grade-4 treatment-related adverse events were reported. – by Stacey L. Adams

Lancet. 2009;doi:10.1016/S1470-2045(08)70313-9.

This is a straightforward study that shows that in the couple of days after highly emetogenic chemotherapy, the newer agent, palonosetron, is superior to the older agent, granisetron. The only issue with this finding is that there are other ways of preventing the delayed nausea and vomiting which weren’t included in the study. The bottom line really becomes cost and patient convenience. There is a large cost difference between the two drugs. In this country palonosetron is three times the cost, and at the higher doses used in this study would be nearly 10 times the cost of granisetron. It is difficult to decide how much added cost the added benefit is worth. In a simple head-to-head comparison of two drugs in this class, the newer one is better at preventing delayed nausea, and that’s consistent with prior studies. But there are so many anti-emetic choices these days it’s hard to parse out all of the various combinations to decide which is optimal.

– Edward Greeno, MD

Associate Professor of Medicine, Medical Director of the Hematology/Oncology Clinic
The University of Minnesota