Assessment of Nausea and Vomiting Control with Aprepitant in High-Dose Melphalan Stem Cell Transplantation

Background: Chemotherapy-induced nausea and vomiting can adversely affect patients’ health and quality of life. Guidelines recommend prophylactic antiemetic regimens according to the emetogenic potential of anti-tumor therapies. However, these recommendations are not for patients receiving high-dose myeloablative regimens prior to stem cell transplant (SCT). Current guidelines do not recommend a specific antiemetic regimen for patients receiving high-dose chemotherapy prior to SCT due to a lack of evidence. At VCUHS, the standard of care in patients receiving high-dose melphalan prior to SCT was an antiemetic regimen consisting of ondansetron + dexamethasone. Due to perceived poor nausea and vomiting control, the standard of care was changed in August of 2012 to a three-drug regimen containing aprepitant. Following this change in practice, this project was undertaken for the primary objective of determining the effectiveness of an antiemetic regimen containing aprepitant compared to the previous standard of care in patients receiving high-dose melphalan prior to autologous SCT.

Methods: This retrospective observational review compared patients who received the previous antiemetic standard of care to those who received the three-drug regimen containing aprepitant prior to autologous SCT with high-dose melphalan conditioning at VCUHS between April 2010 and April 2013. The primary outcome measure was overall nausea control (NC), defined as no episodes of documented emesis and ≤ 2 uses of rescue antiemetics in the overall phase (D-2 to D+2) with no additional scheduled antiemetics.

Results: 114 patients were included in the analysis. The rate of overall NC was not significantly different between the two groups [treatment difference -1%, 95% CI -19 to 18]. However, the mean number of episodes of emesis was significantly lower in the aprepitant group than in the control group in the acute (0 vs. 0.2, p = 0.012), delayed (0.3 vs. 1.3, p < 0.001), and overall period (0.3 vs. 1.4, p < 0.001). Also, fewer patients in the aprepitant group required additional scheduled antiemetics (3% vs. 36%, p = 0.011) than patients in the control group. There were no significant differences in length of stay or time to neutrophil engraftment.

Conclusions: The addition of aprepitant failed to demonstrate a statistically significant benefit in terms of overall NC when compared to the previous antiemetic standard of care in patients receiving high-dose melphalan prior to autologous SCT. This lack of benefit and lower than expected rates of overall NC were attributed to aggressive pre-emptive rescue antiemetic use and additional doses of scheduled ondansetron in the control group. However, this analysis did find that aprepitant reduces episodes of emesis and use of additional scheduled antiemetics in patients receiving high-dose melphalan prior to autologous SCT.