Texas Children's Hospital/Baylor College of Medicine, Houston, Texas.
St Jude Children's Research Hospital, Memphis, Tennessee.
Neuro Oncol. 2020 Jun 9;22(6):875-885. doi: 10.1093/neuonc/noaa016.
A Pediatric Brain Tumor Consortium (PBTC) phase I/II trial of veliparib and radiation followed by veliparib and temozolomide (TMZ) was conducted in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). The objectives were to: (i) estimate the recommended phase II dose (RP2D) of veliparib with concurrent radiation; (ii) evaluate the pharmacokinetic parameters of veliparib during radiation; (iii) evaluate feasibility of intrapatient TMZ dose escalation; (iv) describe toxicities of protocol therapy; and (v) estimate the overall survival distribution compared with historical series.
Veliparib was given Monday through Friday b.i.d. during radiation followed by a 4-week rest. Patients then received veliparib at 25 mg/m2 b.i.d. and TMZ 135 mg/m2 daily for 5 days every 28 days. Intrapatient dose escalation of TMZ was investigated for patients experiencing minimal toxicity.
Sixty-six patients (65 eligible) were enrolled. The RP2D of veliparib was 65 mg/m2 b.i.d. with radiation. Dose-limiting toxicities during radiation with veliparib therapy included: grade 2 intratumoral hemorrhage (n = 1), grade 3 maculopapular rash (n = 2), and grade 3 nervous system disorder (generalized neurologic deterioration) (n = 1). Intrapatient TMZ dose escalation during maintenance was not tolerated. Following a planned interim analysis, it was concluded that this treatment did not show a survival benefit compared with PBTC historical controls, and accrual was stopped for futility. The 1- and 2-year overall survival rates were 37.2% (SE 7%) and 5.3% (SE 3%), respectively.
Addition of veliparib to radiation followed by TMZ and veliparib was tolerated but did not improve survival for patients with newly diagnosed DIPG.
NCT01514201.
儿科脑肿瘤联盟（PBTC）进行了一项 I/II 期试验，在新诊断为弥漫性内在脑桥胶质瘤（DIPG）的儿童中，使用维利帕利（veliparib）联合放疗，随后使用维利帕利联合替莫唑胺（TMZ）。目的是：（i）评估维利帕利与放疗同时使用的推荐 II 期剂量（RP2D）；（ii）评估维利帕利在放疗期间的药代动力学参数；（iii）评估患者内 TMZ 剂量递增的可行性；（iv）描述方案治疗的毒性；（v）与历史系列相比，估计总生存分布。
维利帕利在放疗期间每周一至周五每日两次（bid）给药，随后休息 4 周。然后，患者接受维利帕利 25mg/m2 bid 和替莫唑胺 135mg/m2 每日一次，每 28 天 5 天。对经历最小毒性的患者进行 TMZ 患者内剂量递增的研究。
66 名患者（65 名符合条件）入组。维利帕利的 RP2D 为 65mg/m2 bid 与放疗联合使用。维利帕利联合放疗期间出现剂量限制毒性的有：2 级肿瘤内出血（n=1）、3 级斑丘疹（n=2）和 3 级神经系统疾病（全身性神经恶化）（n=1）。维持治疗期间患者内 TMZ 剂量递增不能耐受。在计划的中期分析后，得出结论，与 PBTC 历史对照相比，这种治疗方法并没有显示出生存获益，因此为了无效而停止了入组。1 年和 2 年总生存率分别为 37.2%（SE 7%）和 5.3%（SE 3%）。
维利帕利联合放疗随后使用 TMZ 和维利帕利治疗新诊断的 DIPG 患者是可以耐受的，但不能提高生存率。
NCT01514201。
