Evaluating Methotrexate Treatment in Patients With Low-Risk Postmolar Gestational Trophoblastic Neoplasia

Abstract

The response of low-risk persistent gestational trophoblastic neoplasia (GTN) to methotrexate (MTX) monotherapy is close to 100%. With use of various MTX regimens, 48%–92% of patients go into remission. There is limited data on potential clinical risk factors indicating the need for additional courses of MTX or alternative chemotherapy following an initial course of MTX. This retrospective observational study identified possible clinical factors predictive of the requirement for additional MTX or alternative chemotherapy to obtain a remission in patients with postmolar low-risk GTN who had received MTX initially. Data was analyzed for 1801 women diagnosed with molar pregnancies between 1973 and 2003. Of the 150 women in the final study population, 110 had been diagnosed as complete mole and 40 as partial mole, and all had received MTX as initial therapy for GTN. All women had low-risk disease according to the combined International Federation of Obstetrics and Gynecology (FIGO) stage and the World Health Organization prognostic scores. Remission was defined as achievement and maintenance of undetectable serum beta human chorionic gonadotropin (β-hCG) levels for 1 year. All 150 patients ultimately achieved remission. Of the 70 women (47%) requiring additional courses of chemotherapy including MTX, 45 (64%) required alternative chemotherapy. Multivariate analysis showed that independent prognostic factors predicting increased risk of requiring additional MTX or alternative chemotherapy were complete mole histology, presence of metastasis, single day MTX infusion and any increase in β-hCG levels 1 week after MTX therapy. Dilatation and curettage within 1 week after the diagnosis of persistence was not an independent risk factor for additional or alternative chemotherapy. For GTN following complete mole, β-hCG levels ≥2000 mIU/ml at 1 week post-MTX were associated with an 89% risk of requiring additional MTX chemotherapy and a 64% risk of alternative chemotherapy to achieve remission. These data identify several independent risk factors that predispose women with low-risk GTN to require additional MTX cycles and alternative chemotherapy after initial MTX.