Phase 1 Study of an Oxaliplatin and Etoposide Regimen in Pediatric Patients With Recurrent Solid Tumors
Phase 1 Study of an Oxaliplatin and Etoposide Regimen in Pediatric Patients With Recurrent Solid Tumors
复制标题
DOI：
10.1002/cncr.24054
复制
发表时间：
2009-02-01
期刊：
影响因子：
6.2
通讯作者：
Fouladi, Maryam
中科院分区：
文献类型：
--
作者：
McGregor, Lisa M.;Spunt, Sheri L.;Fouladi, Maryam
背景：铂类药物和依托泊苷的联合应用已在多种儿科肿瘤中诱导了反应。这项研究估计了奥沙利铂和依托泊苷方案在复发实体瘤儿童中的最大耐受量(MTD)。方法：奥沙利铂第1天给药，依托泊苷第1~3天给药。3~6例患者分为3个剂量水平：1)奥沙利铂130 mg/m(2)+依托泊苷75 mg/m(2)，2)奥沙利铂130 mg/m(2)+依托泊苷100 mg/m(2)，3)奥沙利铂145 mg/m(2)+依托泊苷100 mg/m(2)。钙和镁的输注剂量水平为3，试图将奥沙利铂剂量提高到超过单药MTD的水平。结果：16例患者共接受63个疗程。在剂量水平1，6名患者中有1名出现限量性鼻出血、神经病变和中性粒细胞减少。剂量水平2(n=6)未出现剂量限制性毒性(DLT)。在剂量水平3，4名患者中有2名出现剂量限制性中性粒细胞减少；无1名患者出现3级或4级急性神经病变。6名患者因急性感觉神经病需要延长奥沙利铂输注时间。在髓母细胞瘤(1例完全缓解)和松果体母细胞瘤(1例部分缓解)患者中观察到反应；其他3例不典型畸胎样横纹肌瘤、室管膜瘤和软组织肉瘤患者的病情稳定时间延长。结论：该方案的MTD为奥沙利铂130 mg/m(2)，第1天给药；依托泊苷100 mg/m(2)/d，第1~3天给药，中性粒细胞减少为DLT。钙和镁的输注不允许奥沙利铂剂量的增加。该组合耐受性良好，并显示出抗肿瘤活性。《癌症》2009；115：655--。(C)2008年美国癌症协会。
BACKGROUND: The combination of a platinating agent and etoposide has induced responses in various pediatric tumors. The study estimated the maximum tolerated dose (MTD) of an oxaliplatin and etoposide regimen in children with recurrent solid tumors. METHODS: Oxaliplatin was administered on Day 1 and etoposide on Days 1 to 3 of each 21-day course. Cohorts of 3 to 6 patients were enrolled at 3 dose levels: 1) oxaliplatin at a dose of 130 mg/m(2) and etoposide at a dose of 75 mg/m(2), 2) oxaliplatin at a dose of 130 mg/m(2) and etoposide at a dose of 100 mg/m(2), and 3) oxaliplatin at a dose of 145 mg/m(2) and etoposide at a dose of 100 mg/m(2). Calcium and magnesium infusions were used at dose level 3 in an attempt to escalate the oxaliplatin dose past the single-agent MTD. RESULTS: The 16 patients received a total of 63 courses. At dose level 1, dose-limiting epistaxis, neuropathy, and neutropenia occurred in 1 of 6 patients. No dose-limiting toxicity (DLT) occurred at dose level 2 (n = 6). At dose level 3, 2 of 4 patients experienced dose-limiting neutropenia; none experienced grade 3 or 4 acute neuropathy. Six patients required prolongation of the oxaliplatin infusion because of acute sensory neuropathy. Responses were observed in patients with medulloblastoma (1 complete response) and pineoblastoma (1 partial response); 3 others with atypical teratoid rhabdoid tumor, ependymoma, and soft tissue sarcoma had prolonged disease stabilization. CONCLUSIONS: The MTD of this regimen was found to be oxaliplatin at a dose of 130 mg/m(2) given on Day 1 and etoposide at a dose of 100 mg/m(2)/d given on Days 1 to 3. Neutropenia was found to be the DLT. Calcium and magnesium infusions did not allow escalation of the oxaliplatin dose. The combination was well-tolerated and demonstrated antitumor activity. Cancer 2009;115:655-64. (c) 2008 American Cancer Society.