Stiff, P.J., Fox-Geiman, M.P., Kiley, K., Rychlik, K., Parthasarathy, M., Fletcher-Gonzalez, D., … Rodriguez, T.E. (2013). Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens. Biology of Blood and Marrow Transplantation, 19(1), 49-55.e1.

To evaluate the safety and efficacy of oral aprepitant in combination with ondansetron and dexamethasone in the prevention of acute and delayed nausea and vomiting compared to ondansetron and dexamethasone alone in patients receiving highly emetogenic preparative regimens before autologous or allogeneic stem cell transplant (SCT).

Patients were stratified by gender and randomized to one of two treatments. The aprepitant group received 125 mg oral aprepitant on day one then 80 mg daily during the preparative regimen + 3 days, 7.5 mg dexamethasone IV, and 8 mg ondansetron by mouth every eight hours daily during preparative regimen + 1 day. The placebo group received an oral placebo daily during the preparative regimen + 3 days, 10 mg IV dexamethasone, and 8 mg oral ondansetron every eight hours daily during the preparative regimen +1  day. Lorazepam was used for breakthrough nausea or vomiting. Prochlorperazine was allowed only for repeated episodes of vomiting (defined as more than four episodes in any 12-hour period). The primary objective was complete response (CR) rate, defined as no emesis with no or mild nausea.

• The study was initiated with 181 randomized participants, of which 179 were eligible for analysis.
• The median age was 50 years with a range of 19-79.
• The sample was 57% male and 33% female.
• Cancer diagnoses were non-Hodgkin lymphoma (32%), acute myeloid leukemia (26%), multiple myeloma (19%), acute lymphoblastic leukemia (7%), Hodgkin lymphoma (7%), chronic myeloid leukemia (3%), and other (6%).
• Treatment groups were stratified based on gender and were balanced with respect to age, weight, and history of nausea and vomiting with prior chemotherapy. Graft type was comparable, however, autoperipheral blood progenitor cell transplantation (PBPCT) represented 53% in the placebo group and 44% in the aprepitant group.

The study was conducted at Loyola University Medical Center Cardinal Bernardin Cancer Center in Maywood, IL.

All patients were in active antitumor treatment.

This study was a single center, comparative (placebo controlled), randomized, double-blind, phase III trial.

Patients rated the number of emetic episodes and nausea severity on a 100-mm visual analog scale (VAS).

• Patients who received aprepitant had significantly higher CR rates (81.9% versus 65.8%; p < 0.001) and significantly better complete control (CC) of vomiting  (73.3% versus 22.5%; p = 0.001) compared to the standard ondansetron plus dexamethasone treatment.
• The percentage of days with one episode of emesis with major efficacy and less than grade 4 nausea was significantly higher in the aprepitant arm (p < 0.001), while those with a minor response or failed was significantly higher in the control arm.
• Fewer total rescue doses were given in the aprepitant arm than in the control arm (594 versus 852; p = 0.033).
• The majority of patients, in both arms, used lorazepam for breakthrough therapy (p = 0.979).
• Aprepitant did not have a negative effect on engraftment. Median time for engraftment and platelet recovery was similar (p =  0.778 and p = 0.8206, respectively).
• A nonsignificant, higher tacrolimus level was noted in the aprepitant group; however, this was not enough to recommend adjustment of standard dosing (p = 0.5858).

Aprepitant in combination with dexamethasone and ondansetron significantly decreased emesis and significant nausea, without an increase in regimen-related toxicities. The regimen did not affect short-term survival and had no significant impact on the use of as-needed antiemetics or overall nausea scores. It did not negatively affect patient outcomes.

Five myeloablative high-dose cyclophosphamide preparative regimens were used. Only two regimens included total body irradiation (TBI), which is thought to cause more nausea.

Similar to standard-dose chemotherapy regimens, aprepitant demonstrated a much higher impact on emesis than it did on nausea. Aprepitant in combination with dexamethasone and ondansetron significantly decreased emesis and significant nausea, without increasing toxicities or affecting short-term survival; the regimen had no significant impact on the use of as-needed antiemetics or overall nausea scores.  Findings suggest that aprepitant assisted in control of nausea as well as emesis.