M-EA (methotrexate, etoposide, dactinomycin) and EMA-CO (methotrexate, etoposide, dactinomycin / cyclophosphamide, vincristine) regimens as first line treatment of high-risk Gestational Trophoblastic Neoplasia.

Singh, Kam; Gillett, Sarah; Ireson, Jane; Hills, Anne; Tidy, John A; Coleman, Robert E; Hancock, Barry W; Winter, Matthew C

High-risk GTN is highly chemo-sensitive with an excellent prognosis with treatment. Historically in the UK, the high-risk regimens used have been M-EA (Sheffield) and EMA-CO (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 1998-2018. 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 hCG complete response (CR) rate was 84.7% (n=50/59). 2 patients died of drug-resistant disease after several lines of multi-agent 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. GCSF, 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. This article is protected by copyright. All rights reserved.