Phase I study of weekly oxaliplatin in relapsed or refractory pediatric solid malignancies
Phase I study of weekly oxaliplatin in relapsed or refractory pediatric solid malignancies
复制标题
DOI：
10.1200/jco.2008.16.7585
复制
发表时间：
2008-09-20
影响因子：
45.3
通讯作者：
Vassal, Gilles
中科院分区：
文献类型：
--
作者：
Geoerger, Birgit;Doz, Francois;Vassal, Gilles
PurposeTo探讨的可行性，最大耐受剂量（MTD），和推荐剂量（RD）的第二阶段研究每周奥沙利铂治疗复发性或难治性儿科实体malignancy.Patients和MethodsEligible患者6个月至21岁，有一个诊断为实体恶性肿瘤，并经历了治疗失败，至少有两个或两个以上的治疗前线。I期研究是多中心、开放标签和非随机的。它预见了两个阶段：剂量递增阶段（包括6个水平），以发现RD，以及RD的扩展阶段，以评价累积毒性。奥沙利铂静脉给药2小时以上的第1天，第8和第15天的28天cycle.ResultsForty-five例患者入组：29例在剂量递增阶段和16例在RD的扩展。中位年龄分别为9.5岁（范围：2.8 - 20.0岁）和7.8岁（范围：1.8 - 19.2岁）。第一个治疗周期的剂量限制性毒性为50 mg/m2时的3级（G（3））脓毒症、90 mg/m2时的G3感觉迟钝、110 mg/m2时的G3感觉迟钝和G3感觉异常，因此MTD和RD为90 mg/m2。未报告耳毒性病例。7例患者（16.3%）病情稳定，并确认部分反应观察到2例（4.7%），一个神经母细胞瘤和一个骨肉瘤。ConclusionOxaliplatin管理在每周一次的时间表有一个可以接受的安全性，不同的顺铂和卡铂，并显示活动在儿童复发性或难治性实体瘤，这表明在儿科恶性肿瘤的进一步调查。
PurposeTo explore feasibility, maximum-tolerated dose (MTD), and recommended dose (RD) for phase II studies of weekly oxaliplatin for the treatment of relapsed or refractory pediatric solid malignancies.Patients and MethodsEligible patients were 6 months to 21 years old, had a diagnosis of a solid malignancy, and had experienced treatment failure with at least two or more previous lines of therapy. The phase I study was multicentric, open-label, and nonrandomized. It foresaw two phases: a dose-escalation phase (comprising six levels) to find the RD and an extension at the RD to evaluate the cumulative toxicity. Oxaliplatin was administered intravenously over 2 hours on days 1, 8, and 15 of a 28-day cycle.ResultsForty-five patients were enrolled: 29 patients in the dose-escalation phase and 16 patients in the extension at the RD. Median age was 9.5 years (range, 2.8 to 20.0 years) and 7.8 years (range, 1.8 to 19.2 years), respectively. The dose-limiting toxicities during the first treatment cycle were grade 3 (G(3)) sepsis at 50 mg/m(2), G3 dysesthesia at 90 mg/m(2), and G3 dysesthesia and G3 paresthesia at 110 mg/m(2), thus the MTD and RD was 90 mg/m(2). No case of ototoxicity was reported. Stable disease was reported in seven patients (16.3%), and confirmed partial response was observed in two patients (4.7%), one with neuroblastoma and one with osteosarcoma.ConclusionOxaliplatin administered in a weekly schedule has an acceptable safety profile, different from cisplatin and carboplatin, and shows activity in children with relapsed or refractory solid tumors, suggesting further investigation in pediatric malignancies.