Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study. Actinomycin d versus methotrexate-folinic acid as the treatment of stage I, low-risk gestational trophoblastic neoplasia: a randomized controlled trial. Pulse methotrexate versus pulse actinomycin D in the treatment of low-risk gestational trophoblastic neoplasia. Comparison of pulse methotrexate and pulse dactinomycin in the treatment of low-risk gestational trophoblastic neoplasia. Comparison of pulsed actinomycin D versus 5-day methotrexate for the treatment of low-risk gestational trophoblastic disease.
There is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia (GTN).
                Two commonly used single-drug regimens were compared with respect to the proportion of patients meeting the criteria for a complete response (CR) in a randomized phase III trial conducted by the Gynecologic Oncology Group. Eligibility was purposefully broad to maximize the generalizability of the results and included patients with a WHO risk score of 0 to 6 and patients with metastatic disease (limited to lung lesions < 2 cm, adnexa, or vagina) or choriocarcinoma.
                Two hundred forty women were enrolled, and 216 were deemed eligible. Biweekly intravenous dactinomycin 1.25 mg/m² was statistically superior to weekly intramuscular (IM) methotrexate 30 mg/m² (CR: 70% v 53%; P = .01). Similarly, in patients with low-risk GTN as defined before the 2002 WHO risk score revisions (risk score of 0 to 4 and excluding choriocarcinoma), response was 58% and 73% in the methotrexate and dactinomycin arms, respectively (P = .03). Both regimens were less effective if the WHO risk score was 5 or 6 or if the diagnosis was choriocarcinoma (CR: 9% and 42%, respectively). There were two potential recurrences; one at 4 months (dactinomycin) and one at 22 months (methotrexate). Not all patients completed follow-up. Both regimens were well tolerated.
                The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN, a generally curable disease. This study is to compare the remission and complication rates of actinomycin D (Act-D) and methotrexate-folinic acid (MTX-FA) as single-agent treatments of stage I, low-risk gestational trophoblastic neoplasia (GTN). From 1994 to 2005, all women with International Federation of Gynecology and Obstetrics stage I, low-risk GTN were randomly assigned to received either intravenous Act-D 10 microg/kg per day for 5 days every 2 weeks or intramuscular methotrexate 1 mg/kg per day on days 1, 3, 5, and 7 with intramuscular folinic acid 0.1 mg/kg per day on days 2, 4, 6, and 8 every 2 weeks. Forty-nine women met the eligibility criteria. Age, human chorionic gonadotropin level, and International Federation of Gynecology and Obstetrics score were similar in both treatment groups. Of the 22 women who received Act-D, 2 were lost to follow-up. Among the 27 women who received MTX-FA, 2 were lost to follow-up, and 6 had to switch to Act-D because of the rising levels of liver enzymes. All 20 women (100%) in the Act-D arm achieved remission compared with 14 (73.6%) in 19 women in the MTX-FA arm (P = 0.02). Mucositis and alopecia were reported more frequently in the Act-D group, whereas elevations of liver enzyme levels were more frequent in the MTX-FA group. Actinomycin D seems to be more effective than MTX-FA in the treatment of stage I, low-risk GTN. Larger multicenter randomized controlled trials should be conducted to establish the most appropriate regimen for these patients. To compare the efficacy of methotrexate and actinomycin D as single agents in first-line chemotherapy for women with low-risk gestational trophoblastic neoplasia (LR-GTN).
                A total of 131 women with LR-GTN were randomized to receive a weekly pulsed dose of 30 mg/m(2) of methotrexate intramuscularly (n=81) or a pulsed intravenous bolus of 1.25 mg/m(2) of actinomycin D every 2 weeks (n=50). An additional cycle was administered as consolidation treatment following normalization of the serum level of beta-human chorionic gonadotropin (<5 IU/L).
                Complete remission was achieved in 48.14% of patients in the methotrexate group and 90.00% in the actinomycin D group (P<0.001). The mean number of treatment cycles needed to achieve response was lower in the actinomycin D group (4.8 vs 6.8). The risk of treatment failure was 26.4 greater with methotrexate than with actinomycin D (95% confidence interval, 5.7-22.6; P<0.001).
                Actinomycin D may be a better option than methotrexate as a first-line chemotherapy agent for patients with LR-GTN. Methotrexate and dactinomycin are efficient drugs in the treatment of patients with low-risk gestational trophoblastic neoplasia (LRGTN). To compare the effectiveness of these two drugs in LRGTN, 46 patients were randomised to receive weekly intramuscular methotrexate at 30 mg/m(2) (n = 28) or intravenous dactinomycin at 1.25 mg/m(2) every 2 weeks (n = 18). Fourteen patients (50%) in the methotrexate group and 16 patients (89%) in the dactinomycin group achieved complete response. Greater patient convenience and a lower number of required visits make dactinomycin superior to other alternatives. To determine the effectiveness of 2 standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the International Federation of Gynecology and Obstetrics (FIGO) staging system.
                From 2008 until 2010, 75 women with low-risk gestational trophoblastic disease received either pulsed actinomycin D (n=50) or 5-day methotrexate (n=25). The primary remission rate, the duration of treatment, the number of treatment courses, and the adverse effects were compared.
                The complete remission rates were 90% for the actinomycin D group and 68% for the methotrexate group (P=0.018). The mean number of chemotherapy courses administered to achieve complete remission (including courses of second-line therapy) was 3.1 in the methotrexate group and 5.3 in the actinomycin D group (P=0.01). No major adverse effects were experienced in either treatment group and there were no significant differences in terms of adverse effects. Second-line chemotherapy was indicated for 11 patients.
                Based on the present study, pulsed actinomycin D seems to be an appropriate first-line treatment for patients with low-risk gestational trophoblastic disease.
                Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Dactinomycin is more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, compared with methotrexate. There is limited evidence relating to side-effects, however, the pulsed dactinomycin regimen does not appear to be associated with significantly more side-effects than the low-dose methotrexate regimen and therefore should compare favourably to the five- and eight-day methotrexate regimens in this regard.
We consider pulsed dactinomycin to have a better cure rate than, and a side-effect profile at least equivalent to, methotrexate when used for first-line treatment of low-risk GTN. Data from a large ongoing trial of pulsed dactinomycin compared with five- and eight-day methotrexate regimens is likely to have an important impact on our confidence in these findings.