Pediatric and Adolescent Drug Development, Children and Young People's Unit, The Royal Marsden NHS Foundation Trust - Paediatric Offices, Downs Road, Sutton, SM2 5PT, UK.
Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK.
J Neurooncol. 2018 Mar;137(1):83-92. doi: 10.1007/s11060-017-2698-z. Epub 2017 Dec 13.
Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2 years (range 1.0-17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90-100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9 months with CR/PR, 14.5 months with SD and 3.7 months with progressive disease (p < 0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials.
中枢神经系统 (CNS) 肿瘤是儿科肿瘤学中导致死亡的主要原因。急需新药来提高生存率。我们评估了参加癌症创新治疗儿童 (ITCC) 联盟 I 期试验的 CNS 肿瘤儿童和青少年的结果。在 2000 年至 2014 年期间，在八个 ITCC 中心首次剂量发现试验中登记时年龄<18 岁的患有实体瘤的患者被回顾性纳入。使用单变量/多变量分析评估生存情况。总共纳入了 114 名患者（109 名对疗效进行评估）。中位年龄为 10.2 岁（范围 1.0-17.9）。主要诊断包括：髓母细胞瘤/原始神经外胚层肿瘤（32.5%）和高级别胶质瘤（23.7%）。7.3%的患者报告完全/部分缓解（CR/PR），23.9%的患者疾病稳定（SD）。在单变量分析中，功能状态为 90-100%、上学/工作、正常 ALT/AST 和 CR/PR/SD 与更好的总生存（OS）相关。在多变量分析中，无法评估筛选/入组时的变量与 OS 相关。由于毒性，有 5 名患者（4.5%）退出研究。无因毒性死亡。CR/PR 的中位 OS 为 11.9 个月，SD 为 14.5 个月，进展性疾病为 3.7 个月（p<0.001）。在 I 期试验中招募 CNS 肿瘤儿童和青少年是可行的、安全的，可为患者带来潜在益处。在参加 I 期试验的 CNS 肿瘤儿童中，持续疾病稳定具有作为抗肿瘤活性标志物的潜在作用。
