Oncology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Pediatric Hematology/Oncology Unit, University Hospital La Fe, Valencia, Spain.
Eur J Cancer. 2020 Aug;135:89-97. doi: 10.1016/j.ejca.2020.04.031. Epub 2020 Jun 15.
The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nab-paclitaxel monotherapy was further investigated in this phase II study.
Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m of nab-paclitaxel on days 1, 8 and 15 of each 28-day cycle. The primary end-point was the overall response rate (ORR; complete response [CR] + partial response [PR]). Secondary end-points included duration of response, disease control rate (DCR; CR + PR + stable disease [SD]), progression-free survival, 1-year overall survival, safety and pharmacokinetics.
Forty-two patients were enrolled, 14 each with Ewing sarcoma, neuroblastoma and rhabdomyosarcoma. The ORRs were 0%, 0% and 7.1% (1 confirmed PR), respectively. The DCRs were 30.8% (4 SD), 7.1% (1 SD) and 7.1% (1 confirmed PR and 0 SD) in the Ewing sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. The median progression-free survival was 13.0, 7.4 and 5.1 weeks, respectively, and the 1-year overall survival rates were 48%, 25% and 15%, respectively. The most common grade III/4IVadverse events were haematologic (neutropenia [50%] and anaemia [48%]), and grade III/IV peripheral neuropathy occurred in 2 patients (14%) in the rhabdomyosarcoma group. Pharmacokinetics analyses revealed that paclitaxel tissue distribution was both rapid and extensive.
In this phase II study, limited activity was observed; however, the safety of nab-paclitaxel in paediatric patients was confirmed.
NCT01962103 and EudraCT 2013-000144-26.
一项 I 期/II 期研究的 I 期部分确定了纳布紫杉醇单药治疗复发性或难治性实体瘤儿科患者的推荐 II 期剂量，并确立了其耐受性。本 II 期研究进一步调查了纳布紫杉醇单药的活性和安全性。
患有复发性或难治性尤文肉瘤、神经母细胞瘤或横纹肌肉瘤的儿科患者在每个 28 天周期的第 1、8 和 15 天接受 240mg/m 的纳布紫杉醇。主要终点是总缓解率（CR+PR）。次要终点包括缓解持续时间、疾病控制率（CR+PR+SD）、无进展生存期、1 年总生存率、安全性和药代动力学。
42 名患者入组，每组 14 名分别患有尤文肉瘤、神经母细胞瘤和横纹肌肉瘤。缓解率分别为 0%、0%和 7.1%（1 例完全缓解）。尤文肉瘤、神经母细胞瘤和横纹肌肉瘤组的疾病控制率分别为 30.8%（4 例 SD）、7.1%（1 例 SD）和 7.1%（1 例确认 PR 和 0 SD）。无进展生存期分别为 13.0、7.4 和 5.1 周，1 年总生存率分别为 48%、25%和 15%。最常见的 III/IV 级不良事件为血液学（中性粒细胞减少症[50%]和贫血[48%]），横纹肌肉瘤组有 2 例（14%）发生 III/IV 级周围神经病。药代动力学分析表明，紫杉醇组织分布既迅速又广泛。
在这项 II 期研究中，观察到有限的活性；然而，纳布紫杉醇在儿科患者中的安全性得到了证实。
NCT01962103 和 EudraCT 2013-000144-26。
