Phase III Trial of Weekly Methotrexate or Pulsed Dactinomycin for Low-Risk Gestational Trophoblastic Neoplasia: A Gynecologic Oncology Group Study

Abstract

A B S T R A C T PurposeThere is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia (GTN). Patients and MethodsTwo 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 Ͻ 2 cm, adnexa, or vagina) or choriocarcinoma. ResultsTwo hundred forty women were enrolled, and 216 were deemed eligible. Biweekly intravenous dactinomycin 1.25 mg/m 2 was statistically superior to weekly intramuscular (IM) methotrexate 30 mg/m 2 (CR: 70% v 53%; P ϭ .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 ϭ .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. ConclusionThe biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN, a generally curable disease. J Clin

The management and outcome of women with post-hydatidiform mole ‘low-risk’ gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l−1

“…There is increasing interest in using pulsed or 5-day actinomycin D rather than MTX-FA as the initial therapy for low-risk treatment, as this single-agent alternative may produce a slightly improved chance of inducing remission (Gilani et al, 2005;Osborne et al, 2008;Yarandi et al, 2008). It is also thought that actinomycin D may result in a shorter duration of treatment.…”

Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women

“…A variety of regimens have been developed, in which non-randomized, mostly retrospective studies demonstrate a 50-90% chance of inducing remission 22 . Osborne et al 16 have suggested that pulsed Act-D is more likely to induce remission than weekly MTX but this randomized study has been underpowered. We are waiting for the results of an larger international trial run by the Gynecology Oncology Group in the United States, begun in 2013 (NCT01535053), evaluating quality of life and acceptability of treatment with the objective of helping to define the optimum single-agent approach 17,23 .…”

“…Usually, it is administered using a 5-day EV schedule in the cases of MTX resistance or toxicity 8,11,12 . In order to reduce the high rate and intensity of collateral effects with 5-day Act-D schedule, several authors have investigated the use of the so-called pulsed Act-D regimen 15,16 . When used as first-line ChT for low-risk GTN patients, pulsed Act-D had the following results in 4 studies: mean number of courses was 4.9 -our results, median 2; resistance was 8-24% -our results, 32.9%; and cure rate ranged from 76% (low-risk metastatic GTN) to 86% (non-metastatic GTN) -our results, 67.1%, with most patients in stage I of FIGO 2002 12,13,16 .…”

“…The FIGO 2002 defined that low-risk GTN could be treated with single-agent ChT, resulting in final survival rates approaching 100% 3,7 . Several studies with Methotrexate (MTX) and Actinomycin D (Act-D) protocols have been used for treatment of low-risk GTN [8][9][10][11][12] ; nevertheless, few studies compared these two drugs in the management of low-risk GTN [13][14][15][16] . Osborne et al 16 has recently published a randomized study that suggests that the use of a bolus dose of Act-D every 15 days might be more effective than the administration of a weekly dose of MTX 16 .…”

Efficacy and Risk Factors Associated to Resistance to Single-Agent Chemotherapy in Low-Risk Gestational Trophoblastic Neoplasia

“…In The Cochrane review, Alazzam et al aimed to determine the efficacy and safety of first line chemotherapy in the treatment of low risk GTN [5]. The review included randomised controlled trials (RCTs) [6] [7], quasi-RCTs [8]- [10] and non-RCTs (cohort and case control studies (CCS) [11] [12]) for the treatment of low risk GTN. Eight studies met the review entry criteria (n = 769).…”