5－氟尿嘧啶联合消瘤芥治疗恶性滋养细胞肿瘤的疗效评价

目的：评价５－氟尿嘧啶联合消瘤芥治疗恶性滋养细胞肿瘤的疗效。方法：回顾性分析辽宁省肿瘤医院自１９７９年至１９８８年以５－氟尿嘧啶（５－ＦＵ）与消瘤芥（ＡＴ１２５８）联合用药治疗的１６６例恶性滋养细胞肿瘤患者的近期疗效、副反应及长期随访结果。结果：１３６例侵蚀性葡萄胎中１０９例（８０．１％）及３０例绒癌中２５例（８３．３％）单纯以本方案治愈。本组侵蚀性葡萄胎近期治愈率为１００．０％，５年及１０年累计生存率为１００．０％及９９．３％。绒癌近期治愈率为８６．７％，５年及１０年累计生存率均为８５．８％。本组无一例因化疗副反应或其并发症死亡。结论：５－ＦＵ与ＡＴ１２５８联合用药是治疗恶性滋养细胞肿瘤的有效化疗方案。     

EMA—CO方案治疗高危耐药妊娠滋养细胞肿瘤33例报道

目的 探讨ＥＭＡ－ＣＯ方案治疗高危、耐药妊娠滋养细胞肿瘤的疗效和可行性。方法 统计ＥＭＡ－ＣＯ方案治疗３３例妊娠滋养细胞肿瘤的疗产、毒副反应和化疗剂量强度的实施情况。结果 总有效率７８．７８％（２６／３３）,高危组有效率８８．２３％（１５／１７）,耐药组有效率７３．３３％（１１／１５）;主要毒副反应为骨髓抑制和胃肠道反应,未发生致死毒副反应;按计划实施剂量强度疗程数占５２．６３％,影响剂量强度主要     

PEA方案与5-Fu+KSM方案治疗妊娠滋养细胞肿瘤疗效比较

目的 探讨PEA方案是否可以作为妊娠滋养细胞肿瘤联合化疗一线选择。方法 回顾性分析中国医科大学附属盛京医院2004年7月至2013年5月62例妊娠滋养细胞肿瘤患者,评价顺铂+足叶乙甙+更生霉素（PEA方案,30例）与氟尿嘧啶+更生霉素（5-Fu+KSM,32例）方案的疗效和毒副反应。结果 PEA方案治疗妊娠滋养细胞肿瘤完全缓解率为93.33%,高于5-Fu+KSM方案组（90.63%）（P>0.05）。副反应PEA组Ⅲ～Ⅳ度粒细胞减少、口腔溃疡和腹泻情况明显少于5-Fu+KSM组,差异有统计学意义（P<0.05）。PEA组恶心呕吐和肝功能损伤的发生率及严重程度均低于5-Fu+KSM组（P>0.05）。结论 两方案治疗妊娠滋养细胞肿瘤疗效相当,PEA方案副反应小、疗程短、费用少,可以作为妊娠滋养细胞肿瘤联合化疗一线选择之一。     

BEP方案治疗恶性滋养细胞肿瘤38例临床分析

目的 研究BEP方案治疗妊娠恶性滋养细胞肿瘤的疗效及化疗副反应。方法 1997年1月～2005年8月，采用BEP方案治疗妊娠恶性滋养细胞肿瘤38例，其中初治患者20例，耐药患者15例，复发患者3例。结果 该方案治疗38例妊娠恶性滋养细胞肿瘤患者，36例完全缓解，总完全缓解率为89．47％。其中初治侵蚀性葡萄胎的治愈率为100％，耐药绒癌的完全缓解率为92．31％，复发性妊娠恶性滋养细胞肿瘤的完全缓解率为100％。化疗副反应主要为Ⅰ～Ⅱ级恶心、呕吐和骨髓抑制。结论 采用BEP方案治疗妊娠恶性滋养细胞肿瘤疗效可，对其他药物耐药或复发病例也可获得满意的疗效，化疗副反应轻，患者易接受，值得进一步研究。     

甲氨蝶呤等药物及手术治疗耐药性滋养细胞肿瘤的疗效分析

目的 分析足叶乙甙、甲氨蝶呤、更生霉素、环磷酰胺、长春新碱方案（ＥＭＡ／ＣＯ）治疗耐药性恶性滋养细胞肿瘤的疗效。方法 回顾性分析了５１例耐药性恶性滋养细胞肿瘤患者,采用ＥＭＡ／ＣＯ方案化疗及（或）辅助以手术与超选择性动脉插管灌注化疗后及毒副反应。结果５１例患者经平均６．９个疗程化疗后,３３例获完全缓解（６４．７％）,１４例部分缓解（２７．５％）,４例无效（７．８％）。完全缓解者随访复发率为６．７％     

低危妊娠滋养细胞肿瘤的治疗

针对低危妊娠滋养细胞肿瘤（gestational trophoblastic neoplasia，GTN）的治疗，在国际妇产科联盟（FIGO）指南推荐的化疗基础上，应该再次分层，0～4分选择放线菌素-D（Act-D）或甲氨蝶呤（MTX）单药化疗，根据一些研究报道，Act-D的疗效优于MTX，而且副反应发生率更低；5～6分者目前建议单药化疗，但可放宽联合化疗方案的适应证。化疗期间密切监测疗效，如果单药化疗耐药，可以个体化的更换另一种单药或联合方案。     

FAEV化疗方案治疗高危型耐药性妊娠滋养细胞肿瘤的疗效分析

目的 总结分析氟尿苷＋放线菌素D＋依托泊苷＋长春新碱（FAEV）化疗方案治疗高危型耐药性妊娠滋养细胞肿瘤的疗效。方法 2001年10月至2004年5月,北京协和医院使用FAEV方案治疗高危型耐药性妊娠滋养细胞肿瘤患者共11例,根据国际妇产科联盟（FIGO）预后评分系统（2000年）评分为7—13分（中位数为9分）,所有患者均因对其他化疗方案耐药而改用FAEV方案,随诊时间15—42个月。结果 以FAEV方案治愈7例患者（64％,7／11）;对FAEV方案耐药4例（36％,4／11）,其中2例改用其他化疗方案后获得缓解,2例放弃治疗。11例患者共接受FAEV方案化疗64个疗程,FAEV方案的主要毒副反应为骨髓抑制,需使用粒细胞集落刺激因子的疗程f与98％（63／64）。结论 对于高危型耐药性妊娠滋养细胞肿瘤患者,FAEV化疗方案可作为一种治疗选择。     

依托泊苷联合顺铂治疗高危、耐药及复发性妊娠滋养细胞肿瘤的疗效分析

目的探讨依托泊苷联合顺铂（EP）方案治疗高危、耐药及复发性妊娠滋养细胞肿瘤（GTN）的疗效及安全性。方法回顾性分析接受EP方案化疗的39例GTN患者的临床资料,其中初治高危患者25例,耐药患者9例,复发患者5例。39例患者中10例患者辅以手术治疗,所有患者均随访,观察其疗效及毒副反应,并追踪继发性肿瘤的发生情况和其中30例保留生育功能患者的生育情况。结果39例GTN患者共接受了221个疗程的EP方案化疗,平均疗程数5．7个,总的完全缓解率为74％（29／39）。其中,25例初冶高危患者总疗程数139个,平均疗程数5．6个,19例完全缓解,6例耐药,完全缓解率为76％（19／25）;9例耐药患者化疗总疗程数55个,平均疗程数为6．1个,6例获完全缓解,3例再次耐药,完全缓解率为6／9;5例复发患者化疗总疗程数27个,平均疗程数为5．4个,4例完全缓解,1例耐药死亡,完全缓解率为4／5。该方案主要的毒副反应是骨髓抑制、消化道反应及脱发,骨髓抑制较轻,均为Ⅰ-Ⅲ度,未发生致死性毒副反应。30例保留生育功能患者共获妊娠8例次,其中人工流产2例次,足月妊娠分娩6例次,共获新生儿6个,均无先天性畸形发生,随访期内（随访时间最长者5年）小儿牛长发育正常。所有存活患者尢继发性肿瘤发生。结论EP方案作为一种安全、有效的化疗方案,口丁用于高危、耐药及复发性GTN患者的治疗。     

EMA/EP方案治疗耐药性滋养细胞肿瘤疗效的初步分析

目的 分析足叶乙甙 甲氨蝶呤 放线菌素D／足叶乙甙 顺铂(EMA／EP)方案治疗耐药性恶性滋养细胞肿瘤的疗效。方法 回顾性分析了15例耐药性恶性滋养细胞肿瘤患者,采用EMA／EP方案化疗,部分患者辅以手术或超选择性动脉插管化疗,观察其疗效及毒副反应。结果 15例患者化疗的平均疗程数为6．2个,化疗后11例获完全缓解(73％),3例部分缓解(20％),1例无效(7％)。其中,3例转移性胎盘部位滋养细胞肿瘤(PslTr)经EMA／EP方案治疗后均完全缓解。该方案的主要毒副反应为骨髓抑制及消化道反应。结论 EMA／EP是治疗耐药性恶性滋养细胞肿瘤患者的有效方案。对于转移性PSTT患者EMA／EP可作为首选化疗方案。     

足叶乙甙(Vp16)治疗MTX耐药的低危滋养细胞肿瘤

低危妊娠性滋养细胞肿瘤患者的治疗前景乐观,近期文献报道治愈率达100％。低危患者的传统一线单剂化疗为MTX,但20％～50％患者可能因初治所选用的单剂化疗耐药而需重新选择治疗方案,还有5％的患者不能耐受毒性反应而换药。自1977年证实足叶乙甙(Vp16)治疗恶性滋养细胞肿瘤有效后,现已成为中、高危患者联合化疗中不可缺少的药物。本研究目的在于评价低危滋养细胞肿瘤MTX耐药患者中单剂Vp16的治疗作用。     

Combination chemotherapy with 5-fluorouracil, methotrexate and etoposide for patients with high-risk gestational trophoblastic tumors: a report based on our 11-year clinical experiences

OBJECTIVES: To evaluate the efficacy, toxicity, and survival of patients with high-risk gestational trophoblastic tumors (GTTs) treated with the 5-fluorouracil (5-FU), methotrexate (MTX) and etoposide (VP-16) regimen. METHODS: Between 1992 and 2003, 26 consecutive patients with FIGO-defined high-risk GTTs were treated with 5-FU, MTX and VP-16 regimen. Among them, 9 patients had received prior chemotherapy. Remission rate, causes of treatment failure, and toxicity were analyzed retrospectively. RESULTS: After treatment with 5-FU, MTX and VP-16 regimen, 21 of 26 gained complete respond (80.8%). Two patients were performed adjuvant hysterectomy and both cured ultimately. Five developed resistance (19.2%), and 1 died of widespread metastases (3.8%). All 5 patients who developed resistance were treated with multidrug regimen of etoposide, methotrexate, and actionmycin D alternating with cyclophosphamide and vincristine (the EMA/CO); 4 were salvaged and 1 died of refractory disease. No ones relapsed. WHO grade 4 leukocytopenia and thrombocytopenia with the 5-FU, MTX and VP-16 regimen occurred in 9.0% and 2.4%, respectively, of the total 167 cycles; other toxic effects were acceptable and manageable. With mean follow up of 37 months, neither relapse nor secondary tumor was observed. CONCLUSIONS: According to our 11 years of clinical observation, 5-FU, MTX and VP-16 chemotherapy is one of effective multiagent regimen for patients with high-risk GTTs. Its toxicity is mild and manageable. For patients with high-risk and refractory GTTs, this new triple salvage chemotherapy regimen may be an effective alternative.     

甲氨蝶呤联合足叶乙甙、顺铂治疗绒毛膜癌耐药病例疗效分析

目的分析足叶乙甙、甲氨蝶呤、顺铂(EMP)方案治疗绒癌耐药病例的疗效,评价此方案的临床应用价值.方法回顾性分析了24例绒癌耐药病例应用EMP方案治疗后的临床疗效及毒副反应.结果24例经平均6.4个疗程化疗,15例获完全缓解(62.5%),6例部分缓解(25%),3例无效(12.5%).完全缓解后复发率为6.7%.结论EMP是治疗耐药滋养细胞肿瘤的安全、有效方案.     

Methotrexate infusion and folinic acid as primary therapy for nonmetastatic and low-risk metastatic gestational trophoblastic tumors. 15 years of experience

OBJECTIVE: To investigate the efficacy and toxicity of methotrexate (MTX) given intravenously (i.v.) at a dose of 100 mg/m2 i.v. bolus and 200 mg/m2 infusion over 12 hours followed by folinic acid in the primary treatment of gestational trophoblastic tumors (GTTs). STUDY DESIGN: We reviewed the records of patients at the New England Trophoblastic Disease Center who had received MTX infusion at a dose of 100 mg/m2 i.v. bolus and 200 mg/m2 infusion over 12 hours followed by folinic acid as primary therapy for GTTs that did not resolve with uterine evacuation alone. Data on the patients' age, gravity and parity, disease stage (by FIGO and WHO criteria), antecedent pregnancy, presenting level of hCG, metastatic status, courses of chemotherapy required to achieve remission, toxicity related to chemotherapy treatments and time to normalization of hCG were recorded. RESULTS: One hundred ninety-two patients with persistent GTTs were treated with the MTX infusion protocol between December 1985 and December 2000. One hundred twenty-four patients (64.6%) achieved complete remission with the MTX infusion protocol. Complete remission was induced in 108 (87.1%) with a single course of chemotherapy; 12 others achieved remission with a single additional course of MTX. All patients found to be resistant to MTX therapy later achieved remission with other chemotherapy. Minimal toxicity was experienced during MTX treatment. CONCLUSION: MTX infusion with folinic acid is effective and well tolerated as primary single-agent therapy for nonmetastatic and low-risk metastatic GTT.     

Low-risk gestational trophoblastic neoplasia outcome after treatment with VMP regimen from 2005 to 2017

ObjectiveTo evaluate the efficacy and toxicity of VMP regimen applied to the patients with low-risk gestational trophoblastic neoplasia (LR-GTN) treated in Anhui provincial hospital.Materials and methodsBetween 2005 and 2017, 87 patients with low-risk gestational trophoblastic neoplasia received VMP regimen, consisted of vincristine (VCR), methotrexate (MTX) and platinum (cisplatin, carboplatin or nedaplatin), 68 of whom received VMP as their first-line chemotherapy, and 19 methotrexate-failed patients received VMP regimen as their second-line chemotherapy. The staging and scoring system was based on International Federation of Gynecology and Obstetrics (FIGO 2000) criteria. We describe and analyze their baseline characteristics, remission/resistance/recurrence rates, adverse reactions and prognosis.ResultsThe first-line VMP protocol can achieve an 83.8% remission rate and it tended to develop resistance when the pretreatment β-hCG reaches 7503.5 IU/L, and can achieve complete remission with FAV and EMA-CO as the salvage regimen. Among the 19 methotrexate-failed patients, 2 of whom were yet resistant to VMP regimen, followed by several courses of salvage chemotherapy such as FAV and EMP, and achieved 89.5% remission rate in second-line VMP group. Resistance to this regimen was obviously related with higher pre-treatment HCG whether used as primary or salvage treatment. Severe myelosuppression (grade 3 or 4) was shown in 4 (5.9%) of 68 cases, of which none was grade 4.ConclusionFor patients diagnosed with LR-GTN VMP regimen was a safe and effective treatment with a high rate of remission.     

Experimental combination chemotherapy with vincristine and carboquone in human ovarian cancer transplanted into nude mice

The tumor killing effects of combination chemotherapy with vincristine (VCR) and carboquone (CQ) administrated either simultaneously or sequentially with time intervals of up to 36 hours were studied in serially transplantable human ovarian cancer (JOG-1) in nude mice. Using 3H-thymidine pulse labeling, some tumor cell kinetic parameters were estimated as 13.8 hours for Ts and 42.2 hours of Tc, respectively. The induction of partial synchronization after treating with VCR in vivo was confirmed by estimating both the labeling index and the mitotic index. Sequential treatment with VCR followed by CQ at intervals of 24 hours was the most effective anti-tumor schedule in this treatment system. This sequence of drug administration also resulted in either weight loss nor toxic death of the animals during the schedule. These results indicate that the sequential administration of VCR followed by CQ chemotherapy is strongly recommended for clinical application.     

Polyserositis as an Unusual Sign of Methotrexate Toxicity

We present a 46-year-old patient who underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy for persistent trophoblastic disease. Single-agent chemotherapy with alternate methotrexate 1 mg/kg/day and leucovorin 0.1 mg/kg for 8 days was instituted on the first postoperative day. Various adverse symptomatology developed, culminating in a unique side effect, polyserositis. To the best of our knowledge, the wide spectrum of side effects, the short time lapse after onset of chemotherapy, and their severity are uncommon in a patient receiving her first chemotherapeutic treatment with MTX.     

Metastatic placental site trophoblastic tumor. Report of a case with complete response to chemotherapy

BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasia, commonly insensitive to chemotherapeutic agents. CASE: We report on long-term remission in a patient with metastatic PSTT after etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine combination chemotherapy. The 27-year-old patient with metastatic lung PSTT was alive, without evidence of disease, > 40 months after treatment. CONCLUSION: Treatment with multiagent chemotherapy can produce long-term remission, even in patients with metastatic PSTT.     

25 years' experience in the treatment of gestational trophoblastic neoplasia in Hungary

OBJECTIVE: To review our clinical experience in the treatment of gestational trophoblastic neoplasia (GTN) over the past 25 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2001, we treated 355 patients with GTN. The patients were between 14 and 53 years of age, with an average of 28.3. Primary chemotherapy was selected based on the patient's stage of gestational trophoblastic tumor (GTT) and prognostic score. RESULTS: We found metastases in 49.3% (175 of 355) of our patients. Of 173 patients, 162 (93.2%) achieved remission as a result of methotrexate therapy. In 11 patients (6.8%) complete remission was achieved by combination chemotherapy, in some cases assisted by operation. Of 68 patients, 63 (92.6%) achieved remission as a result of actinomycin D therapy, and 5 (7.4%) achieved complete remission by combination chemotherapy. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% successful therapy in cases of nonmetastatic and low-risk metastatic disease. CONCLUSION: According to our experience, methotrexate/folinic acid or actinomycin D should be the primary treatment in patients with nonmetastatic or low-risk metastatic GTN. Patients with resistance to single-agent chemotherapy regularly achieve remission with combination chemotherapy.