Kilburn Lindsay B, Kocak Mehmet, Baxter Patricia, Poussaint Tina Young, Paulino Arnold C, McIntyre Christine, Lemenuel-Diot Annabelle, Lopez-Diaz Christine, Kun Larry, Chintagumpala Murali, Su Jack M, Broniscer Alberto, Baker Justin N, Hwang Eugene I, Fouladi Maryam, Boyett James M, Blaney Susan M
Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, District of Columbia.
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
Pediatr Blood Cancer. 2018 Feb;65(2). doi: 10.1002/pbc.26832. Epub 2017 Nov 1.
We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG).
Children 3-17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT. Following a 2-week break, three courses of capecitabine, 1,250 mg/m /dose BID for 14 days followed by a 7-day rest, were administered. As prospectively designed, 10 evaluable patients treated at the MTD on the phase I trial were included in the phase II analyses. The design was based on comparison of the PFS distribution to a contemporary historical control (n = 140) with 90% power to detect a 15% absolute improvement in the 1-year PFS with a type-1 error rate, α = 0.10.
Forty-four patients were evaluable for the phase II objectives. Capecitabine and RT was well tolerated with low-grade palmar plantar erythrodyesthesia, increased alanine aminotransferase, cytopenias, and vomiting the most commonly reported toxicities. Findings were significant for earlier progression with 1-year PFS of 7.21% (SE = 3.47%) in the capecitabine-treated cohort versus 15.59% (SE = 3.05%) in the historical control (P = 0.007), but there was no difference for overall survival (OS) distributions (P = 0.30). Tumor enhancement at diagnosis was associated with shorter PFS and OS. Capecitabine was rapidly absorbed and converted to its metabolites.
Capecitabine did not improve the outcome for children with newly diagnosed DIPG.
我们开展了一项II期研究，评估口服卡培他滨速崩片与放射治疗（RT）同时使用时，对新诊断的弥漫性脑桥内在胶质瘤（DIPG）患儿无进展生存期（PFS）的影响。
年龄在3至17岁、新诊断为DIPG的患儿符合入组条件。从放疗第一天开始，给予卡培他滨，剂量为650mg/m²/次，每日两次（同时接受放疗患儿的最大耐受剂量[MTD]），持续9周。休息2周后，给予三个疗程的卡培他滨，剂量为1250mg/m²/次，每日两次，持续14天，随后休息7天。按照前瞻性设计，I期试验中接受MTD治疗的10例可评估患者纳入II期分析。该设计基于将PFS分布与当代历史对照（n = 140）进行比较，检测1年PFS绝对改善15%的检验效能为90%，I类错误率α = 0.10。
44例患者可评估II期研究目标。卡培他滨与放疗耐受性良好，最常报告的毒性反应为轻度手足红斑感觉异常、丙氨酸转氨酶升高、血细胞减少和呕吐。结果显示，卡培他滨治疗组1年PFS为7.21%（标准误 = 3.47%），历史对照组为15.59%（标准误 = 3.05%），早期进展具有显著差异（P = 0.007），但总生存期（OS）分布无差异（P = 0.30）。诊断时肿瘤强化与较短的PFS和OS相关。卡培他滨吸收迅速并转化为其代谢产物。
卡培他滨未能改善新诊断的DIPG患儿的预后。
