EMA/CO for High-Risk Gestational Trophoblastic Neoplasia: Good Outcomes With Induction Low-Dose Etoposide-Cisplatin and Genetic Analysis

Abstract

Patients with high-risk (International Federation of Gynecology and Obstetrics score ≥ 7) gestational trophoblastic neoplasia (GTN) frequently receive etoposide, methotrexate, and dactinomycin alternating weekly with cyclophosphamide and vincristine (EMA/CO). Between 1979 and 1995, overall survival (OS) with this regimen at our institute was 85.4% with a significant proportion of early deaths (< 4 weeks). Here, we determine whether survival rates have improved in a more recent patient cohort (1995 to 2010). Patients receiving EMA/CO were identified using the Charing Cross GTN database. Genetic analysis identified nongestational trophoblastic tumors (nGTTs). The use of induction low-dose etoposide 100 mg/m(2) and cisplatin 20 mg/m(2) (EP; days 1 and 2 every 7 days) since 1995 to reduce early deaths before commencing EMA/CO was noted. Four hundred thirty-eight patients received EMA/CO between 1995 and 2010. Six patients had nGTTs, 140 had high-risk disease, and 250 had relapsed/resistant low-risk GTN. OS was 94.3% in high-risk patients (90.4% including nGTTs) and 99.6% in the low-risk group, with a median follow-up time of 4.2 years. All patients with nGTT and seven patients with high-risk GTNs died as a result of drug-resistant disease. EP induction chemotherapy was given to 23.1% of high-risk patients (33 of 140 patients) with a large disease burden, and the early death rate was only 0.7% (n = 1; 95% CI, 0.1% to 3.7%) compared with 7.2% (n = 11 of 151 patients; 95% CI, 4.1% to 12.6%) in the pre-1995 cohort. OS after EMA/CO for high-risk GTN has increased by nearly 9%. This reflects a more accurate estimate of OS by excluding nGTTs (3.9%) in patients with atypical presentations using genetic diagnosis. Low-dose induction EP in selected individuals also allows near complete elimination of early deaths. The latter should be considered routinely in high-risk GTN.