Pharmacogenetics of Chemotherapy-Induced Nausea and Vomiting

Shigekazu Sugino; Piotr K Janicki


Pharmacogenomics. 2015;16(2):149-160. 

In This Article

Abstract and Introduction


Chemotherapy-induced nausea and vomiting (CINV) is associated with distressing adverse effects observed in patients during cytotoxic chemotherapy. One of the potential factors explaining suboptimal response to currently used antiemetics is variability in genes encoding enzymes and proteins that play a role in the action of antiemetic drugs. Pharmacogenomics studies of CINV are sparse and focus mainly on polymorphisms associated with serotonin receptor, drug metabolism and drug transport. Currently, the role of pharmacogenetics in mechanisms of CINV has not been fully unraveled, and it is premature to implement results of pharmacogenetic association studies of antiemetic drugs in clinical practice. More uniform studies, with genetic profiles and biomarkers relevant for the proposed target and transporter mechanisms, are needed.


Chemotherapy-induced nausea and vomiting (CINV) remains one of the most uncomfortable and distressing adverse effects observed in patients during cytotoxic chemotherapy.[1,2] This adverse event results in expanded care and extension of hospital stay, and thus increases costs for healthcare. Despite appropriate use of antiemetic guidelines, at least 20–30% of patients experience breakthrough nausea and vomiting, secondary to chemotherapy, with highly emetogenic cytotoxic drugs. Increased risk of CINV depends on the type of chemotherapy agents; more than 90% of patients treated with high-risk agents (e.g., cisplatin) experience CINV if no antiemetic drugs are used.[1]

When cisplatin was introduced to clinical use in the late 1970s,[3] CINV was a major problem for the patients undergoing cancer treatment. Many physicians used dopamine D2 receptor antagonists as a first choice for antiemetic therapy. High dose (2 mg/kg) metoclopramide was one such agent tried as a treatment for CINV.[4] However, the clinical significance of D2 receptor antagonists gradually declined as a result of the development of 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists.[5,6] In the 1990s, ondansetron was introduced to the clinical setting and a few additional 'setrons' were also used for CINV, but 5-HT3 receptor antagonists did not have an appreciable effect on CINV at the delayed phase of chemotherapy, 3–5 days after cisplatin.[1,7] Next-generation 5-HT3 (palonosetron) and neurokinin 1 (NK1, aprepitant) receptor antagonists have recently been developed.[8] These drugs are efficient at acting on CINV at the delayed phase of chemotherapy, and have dramatically changed antiemetic therapy for CINV. The established guidelines for management of CINV currently recommend three types of drugs: 5-HT3 receptor antagonists, NK1 receptor antagonists and corticosteroids.[2]