Department of General Pediatrics, Hematology/Oncology, University Children's Hospital Tübingen, Tübingen, Germany.
Department of Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. Von Hauner Children's Hospital, University Hospital, LMU, Munich, Germany.
Drug Des Devel Ther. 2020 Sep 25;14:3915-3927. doi: 10.2147/DDDT.S260887. eCollection 2020.
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.
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) 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).
Clinical adverse events and clinically relevant increases/decreases of laboratory markers were similarly low and did not significantly differ between the two study groups (>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; <0.01), >24-120h (135 vs 78 events; <0.0001), >120-240h (268 vs 105 events; <0.0001), and the whole observation period 0-240h (467 vs 205 events; <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 (>0.05).
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.
高剂量清髓性预处理后自体造血干细胞移植（autoHSCT）在儿科患者中通常具有高度致吐性。神经激肽-1 受体拮抗剂福沙吡坦在接受高致吐性化疗的儿童中是安全有效的。目前尚无儿童接受福沙吡坦预处理的 autoHSCT 数据。
回顾性分析了 35 例连续接受福沙吡坦（4mg/kg；单次剂量，最大 1 x 150mg/kg BW）和昂丹司琼（24 小时持续输注；8-32mg/24h）或格拉司琼（2 x 40μg/kg·d）预防高致吐性预处理化疗后 autoHSCT 的儿科患者的抗呕吐疗效，并且将其结果与仅接受格拉司琼或昂丹司琼的 35 例连续儿科患者的对照组进行比较。比较两种预防方案在首次化疗后三个时间段（0-24 小时、>24-120 小时、>120-240 小时）的抗呕吐疗效和安全性。
临床不良事件和实验室标志物的临床相关升高/降低在两组之间相似且无显著差异（>0.05）。在 0-24 小时（64 比 22 次事件；<0.01）、>24-120 小时（135 比 78 次事件；<0.0001）、>120-240 小时（268 比 105 次事件；<0.0001）和整个观察期 0-240 小时（467 比 205 次事件；<0.0001）中，对照组的呕吐事件发生率显著较高。在>24-120 小时期间，对照组发生呕吐的患者百分比更高（100%比 74.3%），但在其他分析时间期间无显著差异（>0.05）。
福沙吡坦为基础的止吐预防方案是安全的，耐受性良好，并显著减少了接受高致吐性化疗的儿童在接受 autoHSCT 前的呕吐。需要前瞻性随机试验来证实这些结果。
