Aprepitant as Salvage Therapy in Patients with Chemotherapy-Induced Nausea and Emesis Refractory to Prophylaxis with 5-HT₃ Antagonists and Dexamethasone

Abstract

Background: Despite prophylaxis with 5-HT₃ antagonists and dexamethasone, nausea/emesis are common chemotherapy- induced toxicities. The aim of this trial was to evaluate the efficacy of adding the NK1 antagonist aprepitant in patients refractory to standard prophylaxis. Patients and Methods: Patients with significant nausea/vomiting despite prophylaxis with 5-HT₃ antagonists and dexamethasone were eligible. Aprepitant was added to the same antiemetic regimen used during previous cycles. Results: 34 patients received 92 cycles of chemotherapy with aprepitant which was applied orally at 125 mg on day 1 and 80 mg on days 2 and 3. All patients were refractory to standard antiemetic prophylaxis during cisplatin-based (n = 12) or other chemotherapy (n = 22). With the addition of aprepitant, all patients reported subjective improvement. The number of patients with nausea for >4 days decreased from 24 (71%) to 4 (12%) (p < 0.001), and the number of those with emesis for >2 days decreased from 26 (77%) to 0 (0%) (p < 0.001). In 12 patients receiving aprepitant for >2 cycles (3-8) the efficacy was maintained. No toxicity possibly related to aprepitant was observed. Conclusion: Aprepitant demonstrated significant activity in patients with nausea/vomiting refractory to prophylaxis with 5-HT₃ antagonists and dexamethasone.

Chemotherapy-Induced Nausea and Vomiting in the Treatment of Gastrointestinal Tumors and Secondary Prophylaxis with Aprepitant

“…It is important to emphasize that the number of analyzable patients treated by aprepitant is very small. Nevertheless, this is in line with results from a trial conducted by Oechsle et al [20] where aprepitant demonstrated significant activity in patients with nausea/vomiting refractory to prophylaxis with 5HT 3 antagonists and dexamethasone treated with cisplatin-based chemotherapy. The number of patients with nausea for > 4 days decreased from 71 to 12% (p < 0.001), and the number of those with emesis for > 2 days decreased from 77 to 0% (p < 0.001).…”

Aprepitant as salvage antiemetic therapy in breast cancer patients receiving doxorubicin and cyclophosphamide

“…Recently, another report has appeared noting improved antiemetic control with the addition of aprepitant in patients experiencing breakthrough emesis despite receiving prophylaxis with a 5-HT 3 antagonist and dexamethasone during their initial cycle of chemotherapy [25]. In 34 patients receiving a variety of chemotherapy regimens, the addition of aprepitant to the same antiemetic regimen used during the initial cycle resulted in an improved outcome.…”

Antiemetic therapy for multiple-day chemotherapy and additional topics consisting of rescue antiemetics and high-dose chemotherapy with stem cell transplant: review and consensus statement

“…Recent data suggesting that the mechanism of action of palonosetron may differ from that of other serotonin antagonists [22] could provide a rationale for additional activity with this agent. More recently, several studies [23,24] have documented antiemetic activity of the NK-1 antagonists in patients who did not achieve complete protection from emesis when treated with dexamethasone and a serotonin receptor antagonist alone.…”