title: Actinomycin D, cisplatin, and etoposide regimen is associated with almost universal cure in patients with high-risk gestational trophoblastic neoplasia.
abstract: BACKGROUND
  Patients with high-risk gestational trophoblastic neoplasia (GTN) need multi-agent chemotherapy to be cured. The most common regimen is etoposide (E), methotrexate (M) and actinomycin D (A), alternating weekly with cyclophosphamide (C) plus vincristine (O) (EMA/CO). Cisplatin (P) is a very active drug, but it is usually restricted to second-line therapies. Herein, we report the results of a cisplatin-based therapy: APE (actinomycin D, cisplatin, and etoposide).
  
  
  METHODS
  The efficacy and safety of APE for high-risk GTN (defined by Institut Gustave-Roussy (IGR) criteria and/or an International Federation of Gynaecology and Obstetrics (FIGO) score >6) are reported. Patients with brain metastasis or placental-site trophoblastic tumour were excluded.
  
  
  RESULTS
  Between 1985 and 2013, 95 patients were treated with APE for high-risk GTN: 59 patients as first-line, 36 as ⩾ 2nd-line therapy. There was 94.7% complete remission, though five patients relapsed. One patient died from GTN after multiple lines of chemotherapy. The five-year overall survival rate (median follow-up 5.7 years) was 97% (95% confidence interval (CI): 91-99%). No death from toxicity occurred. Long-term, six grade-1 neuro-toxicities, three grade-1 and two grade-2 oto-toxicities, and one grade-1 renal toxicity were recorded. One patient developed AML-M4 after APE and EMA/CO. Thirty-four of 35 women, who wished to become pregnant, succeeded and all had at least one live birth.
  
  
  CONCLUSIONS
  With a 97% long-term overall survival rate, limited long-term toxicity, and an excellent reproductive outcome, APE could be regarded as an alternative option to EMA/CO as a standard therapy for high-risk GTN.
authors.affiliation: Department of Medicine, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Even
authors.affiliation: Department of Medicine, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: P
authors.initials: P
authors.lastname: Pautier
authors.affiliation: Department of Biopathology, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: P
authors.initials: P
authors.lastname: Duvillard
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Floquet
authors.affiliation: Centre Eugène Marquis, Rennes, France.
authors.forename: P
authors.initials: P
authors.lastname: Kerbrat
authors.affiliation: Department of Biopathology, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: F
authors.initials: F
authors.lastname: Troalen
authors.affiliation: Department of Biostatistics, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Rey
authors.affiliation: Department of Radiology, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Balleyguier
authors.affiliation: Department of Medicine, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Tazi
authors.affiliation: Department of Medicine, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Leary
authors.affiliation: Institut de Cancérologie de l'Ouest, Centre Paul Papin, Angers, France.
authors.forename: P
authors.initials: P
authors.lastname: Augereau
authors.affiliation: Department of Surgery, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: P
authors.initials: P
authors.lastname: Morice
authors.affiliation: Centre Léon Bérard, Lyon, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Droz
authors.affiliation: Department of Medicine, Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Department of Medicine, Gustave Roussy, University of Paris Sud, Villejuif, France. Electronic address: catherine.lhomme@igr.fr.
authors.forename: C
authors.initials: C
authors.lastname: Lhommé
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D012074:Remission Induction; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D003609:Dactinomycin; D005047:Etoposide; D002945:Cisplatin
keywords: Actinomycin D; Cisplatin; Etoposide; High-risk gestational trophoblastic neoplasia