替莫唑胺联合托泊替康治疗儿童难治性/复发神经母细胞瘤6例临床分析

Clinical analysis of six cases with refractory or recurrent neuroblastoma treated by combination of topotecan and temozolomide

目的观察替莫唑胺(TMZ)联合托泊替康(TOPO)即TOTEM方案治疗儿童难治性/复发神经母细胞瘤(NB)的疗效。方法 6例难治性/复发NB患儿,分别给予替莫唑胺150 mg/(m^2·d),d1-5,口服;托泊替康0.75 mg/(m^2·d),d1-5,静脉点滴,每3周为一个化疗周期,每个患儿共接受8~10个周期的化疗。治疗中监测血常规、肝功、肾功、心脏功能等;每2个化疗周期行CT或MRI等影像学检查,同时结合骨髓受累病例中微小残留检测结果,进行疗效估。结果 6例NB患儿接受共53个周期TOTEM方案化疗,3例患儿临床达到完全缓解,2例患儿为部分缓解,1例患儿因疾病进展,放弃治疗,本组病人平均随诊时间为15个月,随访1年时4例存活。化疗期间不良反应主要表现为:5例出现Ⅲ°~Ⅳ°骨髓抑制,3例出现Ⅱ°~Ⅲ°恶心、呕吐、厌食,但整个治疗中无化疗相关性死亡病例发生。结论难治性/复发NB患儿对TOTEM方案表现较理想的治疗反应和顺应性,但远期疗效尚待进一步观察,可作为目前治疗儿童难治性/复发NB的选择之一。

Objective To investigate the effect of the combination of topotecan （TOPO） and temozolomide（TOTEM） in the children with refractory or relapsed neuroblastoma.Methods Six children with refractory/relapsed neuroblastoma were analyzed Retrospectively.They were treated by temozolomide,days 1-5,150mg/（m2 ＆#183; d）,orally;topotecan,days 1-5,0.75 mg/（m2 ＆#183; d）,iv,every 3 weeks for a cycle.The total course of treatment for each child for 8-10 cycles.During each cycle of chemotherapy,the general biochemical tests included peripheral blood cell counts,the renal,hepatic and cardiac founctions,etc.Imaging data on computed tomography or MRI was implemented every 2 cycles,with which the treatment responses were evaluated by minimal residual disease of bone marrow involvement cases.Results Totally,6 children received 53 cycles of TOTEM protocol.Three casesachieved complete remission,2 cases achieved partial remission;one case still presented progressive disease after 3 cycles of chemotherapy and quitted.Mean follow-up period was 15 months,4 cases were alive during the 1 years of follow-up.The major of complications during treatment included mo ～ rⅣo myelosuppression （5 cases）,Ⅱ＆#176; ～Ⅲ＆#176; nausea and vomiting （3 cases）,no treatment-related death happened.Conclusions Combination of TOTEM presented favorable treatment response and good compliance on children with primary refractory/relapsed NB,and it can be an efficacious treatment choice,but further study on the long-term efficacy is still needed.