Temozolomide in resistant or relapsed pediatric solid tumors
Temozolomide in resistant or relapsed pediatric solid tumors
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DOI：
10.1002/pbc.20516
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发表时间：
2006-07-01
影响因子：
3.2
通讯作者：
Donfrancesco, A.
中科院分区：
文献类型：
--
作者：
De Sio, L.;Milano, G. M.;Donfrancesco, A.
目的：我们报告了一项说明书外研究，旨在调查替莫唑胺（TMZ）作为单一药物在复发或耐药儿童实体瘤中的应用。对于既往有颅脊髓照射（CSI）或自体骨髓移植（ABMT）的患者，给药剂量为215 mg/m(2)/天× 5天或180 mg/m(2)/天× 5天。患者和方法：纳入52例耐药或复发实体瘤患者，中位年龄127.6个月。肿瘤类型：神经母细胞瘤（NB; n = 17）、髓母细胞瘤（MB; 8）、脑干胶质瘤（BSG; 8）、骨外尤文氏肉瘤/周围神经外胚层瘤（EOES; 4）、尤文氏肉瘤（ES; 4）、间变性星形细胞瘤（AA; 3）、横纹肌肉瘤（RMS; 2）、室管膜瘤（EP; 2）、脑原始神经外胚层瘤（cPNET; 2）、肝癌（HC; 1）、骨肉瘤（OS; 1）。所有患者均进行了预处理。两个门诊疗程，中位数为4.8疗程/次。结果：客观有效率（CR+PR+MR）为13.4% (CR为1.9%，PR为3.8%，MR为7.7%)，SD发生率为38.4%，PD发生率为48%。中位生存期为7.8个月（范围1-37），中位进展时间为3.4个月（范围1-20）；在多变量分析中，这些数据与组织学和既往使用硝基脲有显著相关。21.4%的给药过程出现3-4级血液学毒性（主要是血小板减少），3.1%出现恶心，0.7%出现呼吸窘迫。结论：口服TMZ对耐药或复发的儿童实体瘤具有良好的耐受性，并对标准化疗难治的NB和CNS肿瘤显示出活性。
Purpose: We report the off-label study aimed at investigating the use of temozolomide (TMZ) as single agent in relapsed or resistant pediatric solid tumors. The drug was administered at the dose of 215 mg/m(2)/day x 5 days or 180 mg/m(2)/day x 5 days in patients with prior craniospinal irradiation (CSI) or autologous bone marrow transplantation (ABMT). Patients and Methods: Fifty two patients, median age 127.6 months, with resistant or relapsed solid tumors were enrolled. Tumor types were: neuroblastoma (NB; n = 17), medulloblastoma (MB; 8), brain stem glioma (BSG; 8), extraosseous Ewing's sarcoma/peripheral neuroectodermal tumor (EOES; 4), Ewing's sarcoma (ES; 4), anaplastic astrocytoma (AA; 3), rhabdomyosarcoma (RMS; 2), ependymoma (EP; 2), cerebral primitive neuroectodermal tumor (cPNET; 2), hepatocarcinoma (HC; 1), and osteosarcoma (OS; 1). All patients were pre-treated. Two outpatient courses were administered, with a median of 4.8 courses/pt. Results: Objective response-rate (CR+PR+MR) in our series was 13.4% (1.9% CR, 3.8% PR, and 7.7% MR), SD occurred in 38.4% of patients and 48% had PD. The median survival was 7.8 months (range 1-37) and median time to progression was 3.4 months (range 1-20); these data were significantly correlated with histology and previous nitrosureas administration in multivariate analysis. Haematological toxicity grade 3-4 (mainly thrombocytopenia) was observed in 21.4% of administered courses, nausea was reported in 3.1% and respiratory distress in 0.7%. Conclusion: Oral TMZ was well tolerated in children with resistant or relapsed solid tumors and showed activity in NB and CNS tumours refractory to standard chemotherapy.