Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial

Abstract

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX+ dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference –5.1%, 95% confidence interval (CI) –19.4% to 9.2%, P=0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P=0.577). For the single-course MTX+ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%–36.6%, P<0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P=0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Keywords

gestational trophoblastic neoplasia (GTN) / methotrexate (MTX) / dactinomycin (ACTD)

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Acknowledgements

The work was supported by funding from the Construction of Collaborative Network for Gynecological Tumor Clinical Research (No. 2015BAI13B05), directed by Ding Ma, Academician of the Chinese Academy of Engineering. The research was also supported by funding from the Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province (No. JBZX-201803); Commonweal Technology Research and Social Development Project of Science Technology Development of Zhejiang Province (Nos. 2013C33151 and 2016C33153), and the Zhejiang Medical Science and Technology Development Program (No. 2016KYA123); the National Key Technology R&D Program of China (Nos. 2019YEC1005200 and 2019YEC1005204). We also thank Professor Kun Chen from the Zhejiang University School of Public Health for the reviewing and approving of the statistical analysis.

Compliance with ethics guidelines

Lili Chen , Ling Xi, Jie Jiang, Rutie Yin, Pengpeng Qu, Xiuqin Li, Xiaoyun Wan, Yaxia Chen, Dongxiao Hu, Yuyan Mao, Zimin Pan, Xiaodong Cheng, Xinyu Wang, Qingli Li, Danhui Weng, Xi Zhang, Hong Zhang, Quanhong Ping, Xiaomei Liu, Xing Xie, Beihua Kong, Ding Ma, and Weiguo Lu declare that they have no competing interests. The study was approved by the Ethics Committee of Women’s Hospital of Medicine, Zhejiang University School (date of approval: June 24, 2012), and registered at ClinicalTrials.gov (No. NCT01823315).

Electronic Supplementary Materia

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-021-0855-4 and is accessible for authorized users.

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