Jiang F, Guan C L, Jiao L Z, Xu T, Wan X R, Shi S S, Wu B B, Zhang X, Zhen L, Miao J W, Tian M, Du M, Li C, Feng F Z, Yang J J, Ren T, Zhao J, Li Y, Zhang X Q, Lu X, Xiang Y
Department of Obstetrics & Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, National Clinical Research Centre for Obstetric & Gynecologic Diseases, Beijing, China.
Department of Obstetrics & Gynecology, Gansu Provincial Maternity and Child-care Hospital (Gansu Provincial Central Hospital), Lanzhou City, Gansu Province, China.
Ann Oncol. 2025 Oct;36(10):1123-1131. doi: 10.1016/j.annonc.2025.06.006. Epub 2025 Jun 19.
Cure rates for low-risk gestational trophoblastic neoplasia (GTN) are high, but there is no consensus on optimal first-line chemotherapy. Here we evaluated the efficacy and safety of biweekly single-dose actinomycin D (Act-D) versus an 8-day methotrexate (MTX)-folinic acid regimen as first-line single-agent chemotherapy for low-risk GTN.
This multicenter, randomized, controlled trial enrolled patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-III, low-risk GTN (FIGO 2000 prognostic scores 0-4) across eight centers in China (ClinicalTrials.gov identifier: NCT04562558). Patients were randomized (1 : 1) to Act-D (1.25 mg/m, maximum 2 mg, every 14 days) or MTX-folinic acid (50 mg i.m. days 1, 3, 5, and 7; leucovorin rescue, days 2, 4, 6, and 8). Treatment continued until β-human chorionic gonadotropin normalization, followed by 2-3 consolidation cycles. Primary outcomes were complete remission (CR) rates for single-agent chemotherapy and overall CR rates. Secondary outcomes were time to CR, chemotherapy cycles, toxicity, and anti-Müllerian hormone changes.
Between 27 September 2020, and 18 June 2024, 228 patients were randomized to MTX or Act-D. Act-D achieved significantly higher single-agent CR rates than MTX (72.8% versus 54.4%, P = 0.0038) with shorter median remission time (7.86 versus 9.43 weeks, P = 0.0296). Overall CR rates were 100% in both groups following combination chemotherapy for resistant cases. Most adverse events were grade 1-2, but grade ≥2 nausea and vomiting and hair loss were more frequent with Act-D, and alanine aminotransferase was more frequently elevated in the MTX group. Anti-Müllerian hormone reductions were transient in both groups. After a 28.5-month median follow-up, recurrence rates remained low and comparable (MTX 0.88% versus Act-D 0.88%; P > 0.05). Fertility outcomes were favorable in both groups.
Biweekly Act-D demonstrated superior efficacy and faster remission than the 8-day MTX regimen as first-line single-agent chemotherapy for low-risk GTN, offering a well-tolerated option despite a higher incidence of nausea, vomiting, and hair loss.
低风险妊娠滋养细胞肿瘤（GTN）的治愈率很高，但对于最佳一线化疗方案尚无共识。在此，我们评估了每两周单剂量放线菌素D（Act-D）与8天甲氨蝶呤（MTX）-亚叶酸方案作为低风险GTN一线单药化疗的疗效和安全性。
这项多中心、随机、对照试验纳入了中国8个中心国际妇产科联盟（FIGO）I-III期、低风险GTN（FIGO 2000预后评分0-4）的患者（ClinicalTrials.gov标识符：NCT04562558）。患者被随机（1:1）分为Act-D组（1.25 mg/m²，最大2 mg，每14天一次）或MTX-亚叶酸组（第1、3、5和7天肌内注射50 mg；第2、4、6和8天用亚叶酸解救）。治疗持续至β-人绒毛膜促性腺激素恢复正常，随后进行2-3个巩固周期。主要结局为单药化疗的完全缓解（CR）率和总体CR率。次要结局为达到CR的时间、化疗周期、毒性以及抗苗勒管激素的变化。
在2020年9月27日至2024年6月18日期间，228例患者被随机分为MTX组或Act-D组。Act-D组的单药CR率显著高于MTX组（72.8%对54.4%，P = 0.0038），中位缓解时间更短（7.86周对9.43周，P = 0.0296）。两组对耐药病例进行联合化疗后的总体CR率均为100%。大多数不良事件为1-2级，但Act-D组≥2级恶心、呕吐和脱发更常见，MTX组丙氨酸转氨酶升高更频繁。两组抗苗勒管激素的降低均为短暂性。经过28.5个月的中位随访，复发率仍然很低且相当（MTX组0.88%对Act-D组0.88%；P>0.05）。两组的生育结局均良好。
对于低风险GTN的一线单药化疗，每两周一次的Act-D方案比8天MTX方案显示出更好的疗效和更快的缓解速度，尽管恶心、呕吐和脱发的发生率较高，但仍是一个耐受性良好的选择。
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