Phase II study of vinorelbine and continuous low doses cyclophosphamide in children and young adults with a relapsed or refractory malignant solid tumour: Good tolerance profile and efficacy in rhabdomyosarcoma - A report from the Societe Francaise des Cancers et leucemies de l'Enfant et de l'adolescent (SFCE)
Phase II study of vinorelbine and continuous low doses cyclophosphamide in children and young adults with a relapsed or refractory malignant solid tumour: Good tolerance profile and efficacy in rhabdomyosarcoma - A report from the Societe Francaise des Cancers et leucemies de l'Enfant et de l'adolescent (SFCE)
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DOI：
10.1016/j.ejca.2012.04.012
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发表时间：
2012-10-01
影响因子：
8.4
通讯作者：
Oberlin, Odile
中科院分区：
文献类型：
--
作者：
Minard-Colin, Veronique;Ichante, Jean-Laurent;Oberlin, Odile
目的：这项II期研究评估了静脉注射长春瑞滨（VNL）和连续低剂量口服环磷酰胺（CPM）联合治疗复发性或难治性实体瘤儿童和年轻人的疗效、安全性和药代动力学（PK）特征。共117名患者（中位年龄，12岁）在6个疾病分层中接受静脉注射VNL 25 mg/m2，第1，8，每28天为一周期，15天为一周期，联合每日连续口服CPM 25 mg/m（2）。根据WHO（世界卫生组织）标准，每两个周期评估一次肿瘤缓解。VNL的药代动力学研究在一个子集的18例患者年龄4-15 years.Results：在横纹肌肉瘤（RMS）（n = 50），最佳总反应率（ORR）为36%，4个完全（8%）和14个部分反应（28%）。尤文肉瘤（n = 15）的最佳ORR为13%，非RMS软组织肉瘤（n = 16）为6%，神经母细胞瘤（n = 16）为6%。骨肉瘤（n = 10）和髓母细胞瘤（n = 7）未观察到反应。主要3/4级毒性为中性粒细胞减少（38%）。其他严重毒性有限，周围神经病变发生率为3%，无出血性膀胱炎。PK分析显示，当VNL剂量基于体表面积的dosing.Concluding声明：在重度预治疗的儿童，VNL与CPM相结合，显示出一个有趣的反应率RMS和可接受的毒性特征，支持这些药物在III期试验中的进一步评估，VNL血液暴露于儿童>4岁和成人系列之间。(C)2012爱思唯尔有限公司保留所有权利。
Aim: This phase II study evaluated efficacy, safety and pharmacokinetics (PK) profile of combination intravenous vinorelbine (VNL) and continuous low doses oral cyclophosphamide (CPM) combination in children and young adults with a recurrent or refractory solid tumour.Methods: A total of 117 patients (median age, 12 years) within six disease strata received intravenous VNL 25 mg/m(2) on days 1, 8, and 15 of each 28-day cycle combined with continuous daily oral CPM 25 mg/m(2). Tumour response was assessed every two cycles according to WHO (World Health Organisation) criteria. PK of VNL was investigated in a subset of 18 patients aged 4-15 years.Results: In rhabdomyosarcoma (RMS) (n = 50), the best overall response rate (ORR) was 36% with four complete (8%) and 14 partial responses (28%). The best ORR was 13% in Ewing's sarcoma (n = 15), 6% in non-RMS soft tissue sarcoma (n = 16), and 6% in neuroblastoma (n = 16). No response was observed in osteosarcoma (n = 10) and medulloblastoma (n = 7). The main grade 3/4 toxicity was neutropenia (38%). Other severe toxicities were limited with 3% of peripheral neuropathy and no hemorrhagic cystitis. The PK analysis revealed equivalent blood exposure to VNL between children >4 years and adult series when the VNL dose was based on the body surface area-based dosing.Concluding statement: In heavily pre-treated children, VNL combined with CPM showed an interesting response rate in RMS and an acceptable toxicity profile supporting further evaluation of these agents in phase III trials. (C) 2012 Elsevier Ltd. All rights reserved.