Abstract
Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinical studies on NK1-RAs have shown mixed results in reducing CINV risk. Most studies focused on the use of aprepitant (APR) and casopitant (CAS) in breast cancer patients receiving AC-type (doxorubicin and cyclophosphamide) chemotherapy. In this study, we compared the study design and clinical efficacies of these NK1-RAs in reducing CINV risk. Among the selected eight studies, 4 APR Randomized Controlled Trials (RCTs), 2 APR Observational Studies (OSs) and 2 CAS RCTs were identified. Patient-related characteristics such as the proportion of females (60.0% - 100.0%), age (46.5 - 59.5 years), histories of motion (5.6% - 47.0% in NK1-RA arms) and morning sicknesses (14.2% - 45.0% in NK1-RA arms) and types of antiemetic regimens; as well as chemotherapy-related characteristics such as the proportion of patients on AC chemotherapy (15.0% - 100.0%) varied greatly. In terms of efficacies, both APR and CAS improved overall CR and vomiting in majority of the studies. None of the studies, however, demonstrated that NK1-RA could provide adequate nausea control. To conclude, NK1-RAs are effective in improving vomiting and overall CR, but not useful in controlling nausea or attaining CC, the ideal CINV endpoint. A shift in paradigm is needed for future CINV research. As healthcare providers continue to strive for optimum CINV control in their patients, we hope this review can help them make better informed clinical decisions.
Highlights
Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy [1]
A literature search was conducted in June 2010 on PubMed and the abstract databases of American Society of Clinical Oncology (ASCO), Multinational Association of Supportive Care in Cancer (MASCC), European Cancer Organisation (ECCO) and National Comprehensive Cancer Network (NCCN) using a combination of the keywords “aprepitant”, “casopitant”, “NK-1 antagonists”, “chemotherapy-induced nausea and vomiting”, “AC chemotherapy”, “Adriamycin/doxorubicin”, “epirubicin”, “anthraxcycline”, “cyclophosphamide”, “breast cancer” and “moderately emetogenic”
This review has demonstrated that the Neurokinin-1 receptor antagonists (NK1-RAs) have had success in the clinical management of CINV, in terms of vomiting and breakthrough antiemetics usage (i.e. CR)
Summary
Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy [1]. 40% of patients on moderately emetogenic chemotherapies (MECs) continue to experience CINV [2,3]. Studies have identified a new class of drugs, the neurokinin-1 receptor antagonists (NK1-RAs), to be effective in controlling CINV [4]. Traditional MEC antiemetic regimens entail a 5hydroxytryptamine-3 serotonin receptor antagonist (5HT3RA) and corticosteroid, usually dexamethasone [5,6,7]. While 5HT3-RAs inhibit 5HT3 receptors in the chemoreceptor trigger zone [8] and corticosteroids could possibly prevent emesis by prostaglandin antagonism [9], NK1-RAs have an entirely different mechanism.
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