Department of Gynecological Surgery and Oncology, Obstetrics, University Hospital Lyon Sud, University of Lyon 1.
Department of Medical Oncology, Alliance for Cancer Research, Tenon Hospital, Public Assistance Hospitals of Paris, Paris.
Int J Gynecol Cancer. 2018 Jun;28(5):1038-1044. doi: 10.1097/IGC.0000000000001248.
The objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate.
From 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure.
A total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3-83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post-dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98-50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%).
Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.
本研究旨在评估在一线甲氨蝶呤治疗失败后，采用二线 5 天放线菌素 D 治疗的妊娠滋养细胞肿瘤（GTN）患者的特征和结局。
自 1999 年至 2017 年，在法国滋养细胞疾病参考中心，确定了接受二线放线菌素 D 治疗的甲氨蝶呤耐药 GTN 患者。采用单因素和多因素分析，确定二线放线菌素 D 治疗失败的显著预测因素。
共 877 例 GTN 患者接受一线 8 天甲氨蝶呤治疗，其中 103 例因甲氨蝶呤治疗失败需要二线 5 天放线菌素 D。78 例（75.7%[95%置信区间，66.3%-83.6%]；P<0.0001）完全缓解，而 25 例需要三线治疗，13 例因放线菌素 D 耐药，12 例因放线菌素 D 治疗后复发。接受放线菌素 D 治疗的患者总生存率为 100%。多因素分析显示，在前次妊娠终止至甲氨蝶呤开始之间间隔大于或等于 7 个月是与二线放线菌素 D 治疗失败显著相关的预测因素（确切比值比，9.17[95%置信区间，1.98-50.70]；P=0.0029）。未发生 4 级和 5 级不良事件，最常见的毒性为 1 级恶心（14.6%）。
对于二线治疗的低危甲氨蝶呤失败的 GTN 患者，二线放线菌素 D 治疗的完全缓解率为 75.7%，三线治疗后的总生存率为 100%，因此，无论在开始使用放线菌素 D 时人绒毛膜促性腺激素水平如何，都应优先使用放线菌素 D 作为二线治疗。然而，在前次妊娠终止至甲氨蝶呤开始之间的间隔大于 6 个月，应鼓励考虑替代治疗策略。
