Treatment of Low-Risk Gestational Trophoblastic Neoplasia (FIGO Score 0–6)

There is no consensus on the best chemotherapy regimen for initial management of low-risk gestational trophoblastic neoplasia (GTN), and first-line regimens vary by geography and institutional preference. Most regimens have not been compared head-to-head, and the level of evidence for efficacy is often limited to C2 except as noted below. Even if there are differences in initial remission rate among the regimens, salvage with alternate regimens is very effective, and the ultimate cure rates are generally 99% or more. The initial regimen is generally given until a normal beta human chorionic gonadotropin (beta-hCG) (for the institution) is achieved and sustained for 3 consecutive weeks (or at least for one treatment cycle beyond normalization of the beta-hCG). A salvage regimen is instituted if any of the following occur:

The use of chemotherapy in the first-line management of low-risk GTN has been assessed in a Cochrane Collaboration systematic review.[1] In that systematic review, four randomized controlled trials were identified.[2-5]

Three of the randomized trials [3-5] compared the same two commonly used regimens:

These three trials included a total of 392 patients. In all three trials, patients who received pulsed dactinomycin had better primary complete response rates without the need for additional salvage therapy (relative risk [RR] of cure, 3.00; 95% confidence interval [CI], 1.10–8.17), even though the magnitude of benefit showed substantial heterogeneity (I2 statistic = 79%).[3-5][Level of evidence B1] Fewer courses of dactinomycin therapy were needed to achieve complete response and cure. As expected, salvage chemotherapy was nearly uniformly successful, because almost all low-risk GTN patients are ultimately cured, irrespective of the initial chemotherapeutic regimen. There were no statistically significant differences in most toxicities, including the following:

There was a statistically significant increase in dermatologic toxicity, including alopecia, associated with dactinomycin. However, in the largest study,[5] there was more low-grade gastrointestinal toxicity, grade 2 nausea, grade 1 to 2 vomiting, and grades 1 to 3 neutropenia in the dactinomycin group. These values were statistically significant. In this study, patients with choriocarcinoma and risk scores of 5 to 6 had worse complete response rates to initial treatment with single-agent therapy. Methotrexate was virtually ineffective.[5]

The fourth randomized trial was very small and included 45 patients. The study compared a 5-day regimen of dactinomycin (10 μg/kg) with an 8-day regimen of methotrexate (1 mg/kg) and leucovorin (0.1 mg/kg) on alternate days. There was a statistically significant decrease in risk of failure to achieve primary cure without the need for salvage therapy in the dactinomycin arm (RR, 0.57; 95% CI, 0.40–0.81).[2][Level of evidence B1] There was less alopecia associated with methotrexate but more hepatic toxicity.

The Cochrane systematic review also summarized the evidence from four nonrandomized trials, but comparisons across studies are difficult. The regimens evaluated in those studies are included in the lists below.[1][Level of evidence C2]

Commonly used treatment regimens include the following:

Other regimens in less-common use include the following:[1]

The unusual patient with a tumor that becomes refractory to single-agent chemotherapy is treated with one of the combination regimens described below for high-risk GTN. For more information, see the Treatment of High-Risk Gestational Trophoblastic Neoplasia (FIGO Score ≥7) section.