Efficacy and safety of biweekly single-dose actinomycin D versus multiday methotrexate in low-risk gestational trophoblastic neoplasia: a prospective multicenter randomized trial.

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.

在这里，我们评估了作为低危GTN一线单药化疗方案的每两周一次单剂量放线菌素D（Act-D）与8天甲氨蝶呤（MTX）-亚叶酸方案的疗效和安全性。

patients_and_methods

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).

这项多中心、随机、对照试验在中国的八个中心招募了国际妇产科联盟（FIGO）I-III期、低风险滋养细胞肿瘤（FIGO 2000预后评分0-4）的患者（ClinicalTrials.gov注册号：NCT04562558）。

Patients were randomized (1 : 1) to Act-D (1.25 mg/m2, 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).

患者按1:1的比例随机分配到Act-D组（每14天1.25 mg/m2，最大剂量2 mg）或MTX-叶酸组（第1、3、5、7天肌注50 mg；第2、4、6、8天进行亚叶酸钙解救）。

Treatment continued until β-human chorionic gonadotropin normalization, followed by 2-3 consolidation cycles.

治疗持续至β-人绒毛膜促性腺激素正常化，随后进行2-3个巩固周期。

Primary outcomes were complete remission (CR) rates for single-agent chemotherapy and overall CR rates.

主要结果是单药化疗的完全缓解（CR）率和总体完全缓解率。

Secondary outcomes were time to CR, chemotherapy cycles, toxicity, and anti-Müllerian hormone changes.

次要结果包括达到完全缓解的时间、化疗周期数、毒性反应以及抗穆勒管激素的变化。

Results

Between 27 September 2020, and 18 June 2024, 228 patients were randomized to MTX or Act-D.

从2020年9月27日至2024年6月18日，共有228名患者被随机分配到甲氨蝶呤组或放线菌素D组。

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).

Act-D作为单一药物的完全缓解率显著高于MTX（72.8%对比54.4%，P=0.0038），且中位缓解时间更短（7.86周对比9.43周，P=0.0296）。

Overall CR rates were 100% in both groups following combination chemotherapy for resistant cases.

在对耐药病例进行联合化疗后，两组的总完全缓解率均为100%。

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.

大多数不良事件为1-2级，但Act-D组的≥2级恶心和呕吐以及脱发更为频繁，而MTX组的丙氨酸氨基转移酶升高更为常见。

Anti-Müllerian hormone reductions were transient in both groups.

两组中抗苗勒管激素的降低都是暂时性的。

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).

经过28.5个月的中位随访时间，复发率保持低水平且两组间可比（MTX 0.88% 对比 Act-D 0.88%；P > 0.05）。

Fertility outcomes were favorable in both groups.

两组的生育结果均令人满意。

Conclusions

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 incidenceof nausea, vomiting, and hair loss.

作为低危滋养细胞肿瘤的一线单药化疗，每两周一次的Act-D显示出比8天一次的MTX方案更好的疗效和更快的缓解率，尽管恶心、呕吐和脱发的发生率较高，但它提供了一个耐受性较好的选择。