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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.
AuthorsKam Singh, Sarah Gillett, Jane Ireson, Anne Hills, John A Tidy, Robert E Coleman, Barry W Hancock, Matthew C Winter
JournalInternational journal of cancer (Int J Cancer) Vol. 148 Issue 9 Pg. 2335-2344 (05 01 2021) ISSN: 1097-0215 [Electronic] United States
PMID33210289 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2020 UICC.
Chemical References
  • Dactinomycin
  • Vincristine
  • Etoposide
  • Cyclophosphamide
  • Methotrexate
Topics
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
  • Cyclophosphamide (administration & dosage)
  • Dactinomycin (administration & dosage)
  • Etoposide (administration & dosage)
  • Female
  • Gestational Trophoblastic Disease (drug therapy)
  • Humans
  • Methotrexate (administration & dosage)
  • Pregnancy
  • Risk Factors
  • Vincristine (administration & dosage)

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