ABSTRACT
IMPORTANCE OF THE FIELD: Since the advent of the 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs) in the 1990s, dramatic improvements have been achieved in the field of antiemetic therapy. The enhanced prevention of delayed and overall chemotherapy-induced nausea and vomiting (CINV) offered by palonosetron, a second-generation 5-HT3RA and aprepitant, the first neurokinin-1 receptor antagonists (NK-1RA) represent the only significant treatment advances in the past decade. While initial trials of single-dose palonosetron indicated a potential benefit over first-generation 5-HT3RAs, only recently have new data become available, increasing the weight of evidence distinguishing it as a new 5-HT3RA in the class. AREAS COVERED IN THIS REVIEW: History of antiemetics and palonosetron, including clinical trials and pharmacological research, and literature published between 1981 and 2010 are covered. WHAT THE READER WILL GAIN: Unique pharmacological characteristics of palonosetron exhibiting prolonged half-life, high receptor affinity, allosteric interactions and positive cooperativity with 5-HT3 receptor resulting in long-term alteration and internalization of this receptor may explain the clinical observation of palonosetron. TAKE HOME MESSAGE: This review of recent progress in antiemetic therapy focuses on the newest data on palonosetron and discusses future trials and implications for clinical practice, with the overall goal of learning from history.
