New treatment options for chemotherapy-induced nausea and vomiting.

Significant progress has been made in the development of effective, convenient, and well-tolerated means to prevent nausea and vomiting associated with cancer chemotherapy (CINV). Nevertheless, a substantial minority of patients continues to have suboptimal antiemetic control, and additional treatment approaches are needed. One avenue of investigation being pursued involves the evaluation of a new 5-HT(3) receptor antagonist (palonosetron) that differs from available serotonin antagonists in its markedly longer half-life (40 h) and greater binding affinity for the type-three serotonin receptor. Analysis of available clinical data demonstrates that palonosetron is an active and well tolerated new 5-HT(3) antagonist. Additional studies incorporating dexamethasone and repetitive-day conventional 5-HT(3) antagonist dosing will be necessary to definitively determine the relative efficacy of palonosetron compared to available agents. Another very promising area that moves beyond serotonin focuses on Substance P as a therapeutic target. Substance P is a tachykinin found in neurons in the brainstem. It is the preferred ligand for the neurokinin-1 (NK-1) receptor. Preclinical studies with selective NK-1 antagonists have demonstrated promising antiemetic activity. Subsequent clinical trials with selective NK-1 antagonists for the prevention of CINV have validated the preclinical promise demonstrated with these agents. One agent in this new therapeutic class (aprepitant) recently received regulatory approval in the United States for use in combination with a 5-HT(3) antagonist and dexamethasone, defining a new standard of care for highly-emetogenic chemotherapy.