EMA／CO方案治疗极高危妊娠滋养细胞肿瘤24例临床分析

EMMCO regimen for chemotherapy 24 patients with ultra high-risk gestational trophoblastic neoplasia

目的探讨依托泊苷＋甲氨蝶呤＋放线菌素D（EMA）/环磷酰胺＋长春新碱（CO）方案治疗极高危妊娠滋养细胞肿瘤（GTN）的疗效与副反应。方法收集2001年1月—2015年12月浙江大学医学院附属妇产科医院收治的采用EMA/CO方案化疗、国际妇产科联盟（FIGO，2000年）预后评分≥12分和（或）一线化疗失败的合并脑、肝或广泛转移的极高危GTN患者共24例，随访至2017年12月31日，回顾性分析纳入患者的临床资料，评价EMA/CO方案治疗极高危GTN的疗效与副反应。结果24例极高危GTN患者的预后评分均≥12分（12-18分），中位预后评分为13分。其中，初次化疗者20例（83%，20/24），有化疗失败史者4例（17%，4/24）；伴肝脑转移者7例（29%，7/24），无肝脑转移者17例（71%，17/24）。24例患者接受EMA/CO方案化疗共167个疗程，平均7.0个疗程。其中，16例获完全缓解，完全缓解率为67%（16/24）；耐药8例，耐药率为33%（8/24）。16例获完全缓解的患者中，6例单纯采用EMA/CO方案化疗，10例在EMA/CO方案化疗基础上联合手术治疗。8例EMA/CO方案耐药的患者中，5例改用EMA/依托泊苷＋顺铂（EP）方案并有3例获得缓解，1例改用甲氨蝶呤＋放线菌素D＋环磷酰胺（MAC）方案获得缓解，2例因经济原因放弃治疗。EMA/CO方案化疗的主要副反应为Ⅲ-Ⅳ度中性粒细胞减少、血红蛋白含量降低、脱发，发生率分别为21.6%（36/167）、96.4%（161/167）、60.5%（101/167）。24例极高危GTN患者中，4例死亡（均为耐药患者），达完全缓解的20例患者在随访期内无一例复发，也无一例发生继发性肿瘤。结论EMA/CO方案治疗极高危GTN有效且安全，可作为治疗极高危GTN的选择方法之一。

ObjectiveTo evaluate etoposide, methotrexate and dactinomycin （EMA） /cyclophosphamide and vincristine （CO） regimen for treatment of ultra high-risk gestational trophoblastic neoplasia （GTN） .MethodsA total of twenty-four ultra high-risk patients who had International Federation of Gynecology and Obstetrics （FIGO） prognostic scores greater or equal to 12 with liver, brain, or extensive metastases did poorly when treated with primary chemotherapy admitted in Women′s Hospital, School of Medicine, Zhejiang University from January 2001 to December 2015. All of the patients were treated by EMA/CO regimen and followed up to death or December 2017. The clinical data of patients were analyzed retrospectively and the efficacy and toxicity of EMA/CO were evaluated.ResultsAll of the cases with ultra high-risk GTN had FIGO prognostic scores ≥12 （ranged 12-18, median 13.0） . Twenty patients （83%, 20/24） received EMA/CO regimen as primary treatment and 4 patients （17%, 4/24） had a history of failed chemotherapy. Seven patients （29%, 7/24） had metastasis of liver or brain and 17 patients （71%, 20/24） had no metastasis of liver and brain. Twenty-four patients received totally 167 courses of EMA/CO regimen （average 7.0 courses） . Sixteen patients achieved complete remission and 8 patients showed drug-resistant. The complete remission rate was 67% （16/24） and the resistance rate was 33% （8/24） . Of the 16 patients who got complete remission, 6 cases were treated with EMA/CO regimen alone, and 10 cases were treated by chemotherapy combined with surgery. For the 8 patients who showed drug-resistant to EMA/CO, 5 cases of them received EMA/etoposide and cisplatin （EP） regimen and 3 cases got remission, 1 case received methotrexate, dactinomycin and cyclophosphamide （MAC） regimen and got remission, 2 cases gave up treatment because of economic factors. The side effects of EMA/CO mainly included Ⅲ-Ⅳ degree neutropenia, anemia and alopecia. The incidence of Ⅲ-Ⅳ degree neutropenia during the treatment of EMA/CO was 21.6% （36/167） , the incidence of anemia was 96.4% （161/167） , and the incidence of alopecia was 60.5% （101/167） . In these 24 ultra high-risk GTN patients, 4 patients died during follow-up. In the 20 patients who got complete remission, no recurrence or secondary tumor by chemotherapy were occurred.ConclusionEMA/CO is an effective regimen with manageable toxicity for patients with ultra high-risk GTN.