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. A prospective randomized comparison of methotrexate, dactinomycin, and chlorambucil versus methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine in "poor prognosis" metastatic gestational trophoblastic disease: a Gynecologic Oncology Group study. Treatment of women with disseminated or recurrent advanced ovarian cancer with melphalan alone in combination with 5-fluorouracil and dactinomycin or with the combination of cytoxan, 5-fluorouracil and dactinomycin. Low dose chemotherapy of metastatic breast cancer with cyclophosphamide, adriamycin, methotrexate, 5-fluorouracil (CAMF) versus sequential cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and adriamycin. Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study.
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. In 1981, the Gynecologic Oncology Group initiated a prospective randomized study in which patients with poor-prognosis gestational trophoblastic disease received either standard MAC chemotherapy (methotrexate, dactinomycin, and chlorambucil) or the modified CHAMOMA regimen (methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine). The protocol was closed in May 1986 because the modified CHAMOMA regimen was significantly more toxic and possibly less effective. There were 42 patients entered, with 22 receiving MAC and 20 receiving modified CHAMOMA. There have been six deaths due to disease in the modified CHAMOMA group and none in the MAC group. Five MAC failures and one modified CHAMOMA failure have been rescued by surgery and/or chemotherapy. All six of the patients who died on the modified CHAMOMA regimen had developed disease following a previous term pregnancy, but none had prior chemotherapy. All seven patients who were treated for gestational trophoblastic disease after term pregnancy in the MAC group were cured of disease. With the modified CHAMOMA regimen, 44% of patients had life-threatening hematologic toxicity, as compared with only 9% of the MAC patients. Thus, the standard MAC regimen appears to be at least equally effective and much less toxic than the modified CHAMOMA regimen, indicating a more favorable therapeutic index. The purpose of this study was to determine the efficacy of single and multiple drug chemotherapeutic regimens in the treatment of patients with advanced or recurrent, Stage III and IV, ovarian epithelial carcinoma. Patients were randomly assigned to one of four treatment regimens postoperatively, or at the time of recurrence: Regimen I--Melphalan (MEL) 0.2 mg/kg/day for five days every four weeks; regimen II--MEL as in Regimen I plus 5-fluorouracil (FU) 15 mg/kg/day for five days every four weeks; regimen III--MEL and FU as in regimen II plus dactinomycin (AC) 0.5 mg daily for five days every four weeks; and regimen IV--Cytoxan (CY) 7 mg/kg/day, FU 8 mg/kg/day and AC 0.5 mg/day for five days every four weeks. Four hundred and twenty-seven patients were in the study, 314 of whom are evaluable for progression-free interval (PFI), survival, and toxicity: 102 in regimen I, 80 in regimen II, 83 in regimen III, and 49 in regimen IV. Of these, 293 were considered evaluable for response. Because of excessive toxicity, entry of patients to regimen IV was discontinued midway through the study. The overall toxicity was quite high but was most severe in regimen II and IV where 16 toxicity deaths were recorded. The complete and partial response rate with Melphalan alone was 29.2%. This response rate was not enhanced by the addition of FU or FU and AC and not substantially different than the response rate of AC, FU, and CY. Seventy-eight advanced breast cancer patients with hormone-resistant disease or visceral metastases were randomized to receive either of two low dose regimens consisting of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), and Adriamycin (A) as their initial chemotherapy. One group was treated with CAMF, and the other with CMF until progression, followed by A (CMF leads to A). C was given at 50 mg/m2, po, days 1-14; M at 20 mg/m2, F at 300 mg/m2, and A at 20 mg/m2, iv, days 1 and 8 of each 28-day cycle. The response rates for CAMF vs. CMF did not differ significantly (complete and partial responses-62% vs. 49%; stabilizations-23% vs. 31%). Responses by site of metasis, median times to progression and median survivals were similar for both groups. Poor and good risk partial responders had similar survivals. Twelve percent of CMF patients treated with Adriamycin at the time of progression had partial responses with an associated improved survival. Since CMF is as effective as CAMF, but has less toxicity, low dose therapy with CMF is more acceptable than CAMF as an initial chemotherapy regimen for metastatic breast cancer. Adriamycin may be reserved for subsequent regression induction. The role of corticosteroids in the prophylaxis of graft-versus-host disease (GVHD) is not well established. We have conducted a prospective, randomized, open-label, single-center study about the effect of adding methylprednisolone (MP) to the widely used prophylactic regimen consisting of cyclosporine A and methotrexate. A total of 108 consecutive patients treated with allogeneic bone marrow transplantation from an HLA-identical sibling donor for malignant blood disease were entered into the study; 53 patients were randomized to receive and 55 were randomized not to receive prophylactic MP. The dose of MP was 0.5 mg/kg on days 14 to 20, 1 mg/kg on days 21 to 34, 0.5 mg/kg on days 35 to 48, and thereafter the dose was slowly tapered and the administration discontinued on day 110. In the group given prophylactic MP, the incidence of acute GVHD was lower (19% vs 56%, P =.0001), there was a trend toward a lower incidence of chronic GVHD among low-risk patients (P =.06), and during the first 4 months the time spent at hospital was shorter and there were fewer infections. The total amount of MP given was similar in the study groups because of a higher incidence of acute GVHD and its treatment in the group of patients not given prophylactic MP. There were no significant differences between the study groups in relapse rate or survival. In conclusion, the addition of MP to the combination of cyclosporine and methotrexate markedly reduced the incidence of acute GVHD without causing untoward effects. The timing of corticosteroid administration is probably important for the efficacy.
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.