异环磷酰胺联合卡铂治疗复发和难治性神经母细胞瘤的疗效分析

Efficacy of Chemotherapy Regimen Using Ifosphamide and Carboplatin on Recurrent or Refractory Neuroblastoma

背景与目的:约30%的神经母细胞瘤患者一线化疗疗效欠佳或在治疗中进展,而且尽管采用综合治疗可使晚期神经母细胞瘤患者获得完全缓解(completeresponse,CR),仍有不少患者最终复发。本研究采用异环磷酰胺/卡铂(IC)方案治疗复发和难治性神经母细胞瘤,探讨复发和难治神经母细胞瘤的挽救化疗方案。方法:9例难治和23例复发性神经母细胞瘤患者接受IC方案化疗:卡铂(carboplatin,CBP)400mg/m2静脉滴注,第1天;异环磷酰胺(ifosfamide,IFO)1.5g/m2,静脉滴注,第1～5天,同时予美斯钠解毒,用法为用IFO后第0、4、8h,各静脉注射1次,每次剂量为IFO剂量的20%。每2～3周重复。结果:部分缓解(partialresponse,PR)19例(59.4%),无CR病例。有效患者中位缓解时间4.2(1～28)个月。8例(25%)患者化疗后获得手术切除肿瘤。主要不良反应有:Ⅲ～Ⅳ度白细胞下降发生率44.7%;Ⅲ～Ⅳ度血小板下降发生率53.1%;粒细胞缺乏合并感染发生率18.8%;Ⅰ度肝功能异常发生率12.5%;出血性膀胱炎发生率9.4%。结论:IC方案治疗复发/难治性神经母细胞瘤近期有效率较高,毒性可耐受。但远期预后较差,仍需探讨一些积极有效的治疗方法以提高其远期生存率。

BACKGROUND ＆ OBJECTIVE. About 30% of neuroblastoma patients have poor response to first-line chemotherapy or progress during chemotherapy. Although advanced neuroblastoma patients could achieve complete remission after combined treatment, most of them relapsed finally. This study was to evaluate the efficacy of ifosphamide and carboplatin as a salvage chemotherapy regimen on recurrent or refractory neuroblastoma. METHODS： Nine refractory neuroblastoma patients and 23 recurrent neuroblastoma patients were treated with ifosphamide （1.5 g/m^2 daily for 5 days） and carboplatin （400 mg/m^2 on day 1）. Mesna was applied at a dosage of 20% of ifosfamide 3 times at 4-hour intervals after termination of the ifosfamide infusion. Chemotherapy was administered every 2-3 weeks, RESULTS. None of the 32 patients achieved complete remission; 19（59.4%） achieved partial remission. The median remission time was 4.2 months （1-28 months）. After chemotherapy, 8 patients received operation to resect tumors. Main adverse events included grade Ⅲ～Ⅳ neutropenia （44.7%）, grade Ⅲ～Ⅳ thrombocytopenia （53.1%）, neutropenia accompanied with infection （18.8%）, grade Ⅰ liver dysfunction （12.5%）, and hemorrhagic cystitis （9.4%）. All adverse events were reversible, CONCLUSIONS. Recurrent and refractory neuroblastoma responds well to chemotherapy regimen of ifosphamide plus carboplatin. The toxicities are tolerable. But the long-term prognosis is poor. More effective strategies are needed to improve its longterm survival.