title: EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients.
abstract: OBJECTIVE
  To evaluate the results of etoposide, methotrexate, and dactinomycin alternating with cyclophosphamide and vincristine (EMA/CO) chemotherapy in women with high-risk gestational trophoblastic tumors (GTT) and to document the middle- and long-term toxicity of the regimen.
  
  
  METHODS
  A total of 272 consecutive women with high-risk GTT, including 121 previously treated patients, were treated with weekly EMA/CO. The median follow-up duration is 4.5 years (range, 1 to 16).
  
  
  RESULTS
  The cumulative 5-year survival rate is 86.2% (95% confidence interval, 81.9% to 90.5%). No deaths from GTT have occurred later than 2 years after the end [corrected] of EMA/CO. In a multivariate model, adverse prognostic factors were the presence of liver metastases (P < .0001), interval from antecedent pregnancy (P < .0001), brain metastases (P = .0008), and term delivery of antecedent pregnancy (P = .045). There were 11 (4%) early deaths, while 213 patients (78%) achieved a complete remission. Forty-seven (17%) developed drug resistance to EMA/CO, of whom 33 (70%) were salvaged by further cisplatin-based chemotherapy and surgery. Two women developed acute myeloid leukemia, two cervical malignancy, and one gastric adenocarcinoma after EMA/CO. More than half (56%) of the women who had fertility-conserving surgery and who have been in remission at least 2 years have become pregnant since the completion of EMA/CO, with 112 live births, including three infants with congenital abnormalities.
  
  
  CONCLUSIONS
  EMA/CO is an effective and well-tolerated regimen for high-risk GTT. More than half of the women will retain their fertility; however, there is a small but significant risk of second malignancy.
authors.affiliation: Medical Oncology Unit, Charing Cross Hospital, London, United Kingdom. m.bower@cxwms.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Bower
authors.forename: E S
authors.initials: ES
authors.lastname: Newlands
authors.forename: L
authors.initials: L
authors.lastname: Holden
authors.forename: D
authors.initials: D
authors.lastname: Short
authors.forename: C
authors.initials: C
authors.lastname: Brock
authors.forename: G J
authors.initials: GJ
authors.lastname: Rustin
authors.forename: R H
authors.initials: RH
authors.lastname: Begent
authors.forename: K D
authors.initials: KD
authors.lastname: Bagshawe
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011247:Pregnancy; D012306:Risk; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014328:Trophoblastic Neoplasms / Q000188:drug therapy*; D014594:Uterine Neoplasms / Q000188:drug therapy*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D008727:Methotrexate