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

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with lowrisk 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.