Chemotherapy-induced nausea and vomiting: antiemetic trials that impacted clinical practice.
OBJECTIVE
to review the scientific evidence related to serotonin and substance P and the clinical impact targeting these two neurotransmitters have had managing chemotherapy-induced nausea and vomiting (CINV).


METHODS
a PubMed search (January 1968 to December 2008), restricted to English-language publications, was conducted using the key words antiemetics, cancer chemotherapy, cisplatin, serotonin, substance P, NK(1), and 5-HT(3). Abstracts emanating from the meetings of the American Society of Clinical Oncology and Multinational Association of Supportive Care in Cancer during the period May 2000 to June 2008 were also reviewed.


RESULTS
two important outcomes emanated from well-conducted antiemetic clinical trials (Table 1): first, evidence that serotonin and substance P are major mediators of acute and delayed symptoms and second, improved, though not complete, control of CINV.


CONCLUSIONS
serotonin-type 3 and neurokinin-1 receptor antagonists are the most effective agents currently available. In most cases, these agents are used in conjunction with glucocorticoids. The use of these three types of agents is incorporated into current clinical practice guidelines. Further understanding of the biological and biochemical basis of nausea and vomiting may enhance management of this potentially debilitating adverse effect.
Trigg
Michael E
ME
Global Medical Affairs, Merck & Co., Inc., North Wales, PA 19454, USA. michael_trigg@merck.com
Higa
Gerald M
GM
D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D009325:Nausea / Q000139:chemically induced* / Q000188:drug therapy*; D064729:Neurokinin-1 Receptor Antagonists; D017410:Practice Guidelines as Topic; D012701:Serotonin / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000627:therapeutic use; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy*
D000932:Antiemetics; D000970:Antineoplastic Agents; D005938:Glucocorticoids; D064729:Neurokinin-1 Receptor Antagonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D012701:Serotonin; D013373:Substance P