<p>Antiemetic Prophylaxis with Fosaprepitant and 5-HT₃-Receptor Antagonists in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation</p>

Abstract

Background: High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The antiemetic neurokinin-1 receptor antagonist fosaprepitant was safe and effective in children receiving highly emetogenic chemotherapy. Data on fosaprepitant during autoHSCT in children are currently not available. Methods: A total of 35 consecutive pediatric patients, who received an antiemetic prophylaxis with fosaprepitant (4 mg/kg; single dose, max. 1 x 150 mg/kg BW) and ondansetron (24-hours continuous infusion; 8-32 mg/24h) or granisetron (2 x 40 µg/kg•d −1) during highly emetogenic conditioning chemotherapy before autoHSCT were retrospectively analyzed, and their results were compared with a control group comprising 35 consecutive pediatric patients, who received granisetron or ondansetron only. The antiemetic efficacy and the safety of the two prophylaxis regimens were compared with respect to three time periods after the first chemotherapy administration (0-24h, >24-120h, >120-240h). Results: Clinical adverse events and clinically relevant increases/decreases of laboratory markers were similarly low and did not significantly differ between the two study groups (p>0.05). The registered number of vomiting events was significantly higher in the control group in the time periods of 0-24h (64 vs 22 events; p<0.01), >24-120h (135 vs 78 events; p<0.0001), >120-240h (268 vs 105 events; p<0.0001), and the whole observation period 0-240h (467 vs 205 events; p<0.0001). The percentage of patients experiencing vomiting was higher in the control group during the time period of >24-120h (100% vs 74.3%) but not the other analyzed time periods (p>0.05). Conclusion: The fosaprepitant-based antiemetic prophylaxis was safe, well tolerated and significantly reduced vomiting in children undergoing highly emetogenic chemotherapy prior to autoHSCT. Prospective randomized trials are necessary to confirm these results.

Strategies to Mitigate Chemotherapy and Radiation Toxicities That Affect Eating

“…In the past 25 years, major advances in nausea and vomiting reduction from chemotherapy and/or radiation therapy have improved this situation. These include the following: common use of selective serotonin receptor (5-HT3 also known as 5HT) antagonists for immediate N/V, neurokinin receptor antagonists (aprepitant and fosaprepitant) for delayed nausea, and the recognition of corticosteroids and olanzapine in front-line anti-emetic regimens for chemotherapy and radiation [19,21,[84][85][86][87][88]. Although N/V from chemotherapy and/or radiation remains common, there are many effective strategies to ameliorate N/V and improve eating behaviors during chemotherapy and radiation as detailed in Table 3.…”

“…Extra inflammation may predispose to graft versus host disease (skin, mouth, and GI toxicities). Toxicities can cause eating and activity issues Palifermin [97] and/or a very high level of supportive care (TPN, G-tube or NG tube) [27,85,90,[106][107][108].…”