M-EA (methotrexate, etoposide, dactinomycin) and EMA-CO (methotrexate, etoposide, dactinomycin / cyclophosphamide, vincristine) regimens as first-line treatment of high-risk gestational trophoblastic neoplasia

Abstract

High-risk gestational trophoblastic neoplasia (GTN) is highly chemosensitive with an excellent prognosis with treatment. Historically in the United Kingdom, the high-risk regimens used have been M-EA (methotrexate, etoposide, dactinomycin) (Sheffield) and EMA-CO (methotrexate, etoposide, dactinomycin / cyclophosphamide, vincristine) (Charing Cross, London) with prior published data suggesting no difference in survival between these. Our Sheffield treatment policy changed in 2014, switching from M-EA to EMA-CO, aiming to reduce time in hospital, and harmonise UK practice. We aimed to report the toxicities, response rates and survival outcomes for 79 patients with high-risk GTN treated in the first-line setting with either M-EA (n = 59) or EMA-CO (n = 20) from 1998 to 2018. Median duration of treatment was similar (M-EA, 17.3 weeks (IQR 13.9-22.6) and 17.6 weeks (IQR 13.4-20.7) with EMA-CO. For M-EA, overall human chorionic gonadotrophin (hCG) complete response (CR) rate was 84.7% (n = 50/59). Two patients died of drug-resistant disease after several lines of multiagent chemotherapy; overall survival is 96.6% (median follow-up 10.4 years). For EMA-CO, overall hCG CR rate was 70%, overall survival is 100% (median follow-up 4 years). In our experience, patients treated with EMA-CO experienced an apparent increased incidence of neutropenia, non-neutropenic Grade 3-4 infection, peripheral neuropathy and more treatment delays and nights in hospital. Granulocyte-colony stimulating factor, after both EMA and CO arms, titrated to baseline neutrophil count improved the toxicity profile. Both treatment regimens are associated with excellent prognosis; selection of regimen may be further guided by individual patients' personal, social and family circumstances. There is further rationale to explore whether these regimens can be refined, such as 2-weekly EMA, to optimise patient experience and reduce toxicity while maintaining efficacy.