LeBlanc Zachary C, Clapp Averill, Kaplan Samantha, Shawber Carrie J, Wu June K
Department of Surgery, Columbia University Irving Medical Center, New York, United States.
Department of Obstetrics & Gynecology, Columbia University Irving Medical Center, New York, United States.
Front Pharmacol. 2025 Aug 6;16:1661493. doi: 10.3389/fphar.2025.1661493. eCollection 2025.
Proteasome inhibitors (PIs) are FDA-approved to treat adult malignancies. The PI, Bortezomib (BTZ), has been used off-label in pediatric patients but its safety profile in these patients has yet to be systematically assessed. We sought to review the pediatric safety profile of BTZ based on published clinical articles which we compared to publicly available adult safety data from the BTZ drug insert.
PubMed and the Cochrane Database were searched up through September 2024. We included published clinical studies that reported adverse events (AEs) which included clinical trials, clinical studies (>10 patients), and clinical series/case reports (≤10 patients). Extracted pediatric safety data was compared to reported adult safety profile from the BTZ drug insert.
There was heterogeneity in reporting of different AEs and not all categories were comparable to published adult AEs.any studies were small case series or reports which did not allow for more quantitative analysis. Nevertheless, we found that pediatric patients treated with BTZ reported lower incidence of peripheral neuropathy and gastrointestinal toxicity compared to adults. Rates of bone marrow suppression and infection in pediatrics were comparable to or higher than those observed in adults These incidences were comparable or lower when pediatric patients with leukemia were excluded.
BTZ has an acceptable safety profile for use in pediatric patients. Antibacterial and antifungal prophylaxis should be considered given the high rate of infections.
蛋白酶体抑制剂（PIs）已获美国食品药品监督管理局（FDA）批准用于治疗成人恶性肿瘤。蛋白酶体抑制剂硼替佐米（BTZ）已在儿科患者中使用，但尚未对这些患者的安全性进行系统评估。我们试图根据已发表的临床文章回顾硼替佐米在儿科的安全性，并将其与硼替佐米药品说明书中公开的成人安全性数据进行比较。
检索截至2024年9月的PubMed和Cochrane数据库。我们纳入了报告不良事件（AE）的已发表临床研究，包括临床试验、临床研究（>10例患者）和临床系列/病例报告（≤10例患者）。将提取的儿科安全性数据与硼替佐米药品说明书中报告的成人安全性概况进行比较。
不同不良事件的报告存在异质性，并非所有类别都与已发表的成人不良事件具有可比性。许多研究是小病例系列或报告，无法进行更多定量分析。然而，我们发现，与成人相比，接受硼替佐米治疗的儿科患者外周神经病变和胃肠道毒性的发生率较低。儿科患者的骨髓抑制和感染发生率与成人相当或更高。排除白血病儿科患者后，这些发生率相当或更低。
硼替佐米在儿科患者中的使用具有可接受的安全性。鉴于感染率较高，应考虑进行抗菌和抗真菌预防。
