title: EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital, Imperial College Academic Science National Health Service Trust, London, United Kingdom.
authors.forename: Constantine
authors.initials: C
authors.lastname: Alifrangis
authors.forename: Roshan
authors.initials: R
authors.lastname: Agarwal
authors.forename: Delia
authors.initials: D
authors.lastname: Short
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Fisher
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sebire
authors.forename: Richard
authors.initials: R
authors.lastname: Harvey
authors.forename: Philip M
authors.initials: PM
authors.lastname: Savage
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Seckl
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D011247:Pregnancy; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin; D008727:Methotrexate