Controlling Chemotherapy-Induced Nausea and Vomiting with Neurokinin-1 Receptor Antagonists in Patients on AC-Based Chemotherapy—Are We There Yet?

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.

Palonosetron plus single-dose dexamethasone for the prevention of nausea and vomiting in women receiving anthracycline/cyclophosphamide-containing chemotherapy: meta-analysis of individual patient data examining the effect of age on outcome in two phase III trials

“…Likewise, the overall proportion of younger patients with no vomiting in the palonosetron and 1-day dexamethasone group was consistent with the results observed among younger patients (<55 years) receiving aprepitant for 3 days (70 % vs. 73 %). It also should be noted that optimal nausea control remains an unmeet need in CINV research and the NK-1 receptor antagonists have not been shown to be effective in improving nausea control in patients receiving AC-containing chemotherapy [8, 18]. …”

Supportive Care in Cancer Patients: Current Challenges and Opportunities

“…With the incorporation of supportive care in contemporary cancer treatment over the past two decades, there is a drastic reduction of occurrence of severe toxicities associated with cancer treatment, as well as improvement of patients' quality of life. For example, routine prophylaxis with anti-emetics prior to chemotherapy has greatly reduced the occurrence of chemotherapy-induced nausea and vomiting [2]. Nonetheless, a number of chemotherapy-induced toxicities associated with anti-cancer treatment are still poorly managed in today's clinical practice due to the lack of research in those areas.…”