Treatment of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy

Gynecol Oncol. 2003 Dec;91(3):552-7. doi: 10.1016/j.ygyno.2003.08.028.


Objective: The objective of the study was to evaluate the efficacy and toxicity of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) chemotherapy for the treatment of high-risk gestational trophoblastic neoplasia.

Methods: Forty-five patients with high-risk gestational trophoblastic tumors received 257 EMA-CO treatment cycles between 1986 and 2001. Twenty-five were treated primarily with EMA-CO because of the presence of one or more high-risk factors and 20 were treated with EMA-CO secondarily after failure of single-agent chemotherapy. Patients who had incomplete responses or developed resistance to EMA-CO were treated with drug combinations employing cisplatin and etoposide with or without bleomycin or ifosfamide. Adjuvant surgery and radiotherapy were used in selected patients. Survival, clinical response, and toxicity were analyzed retrospectively.

Results: The overall survival rates was 91% (41/45); survival rates were 92% (23/25) for primary treatment and 90% (18/20) for secondary treatment with EMA-CO. Of the 45 patients treated with EMA-CO, 32 (71%) had a complete clinical response, 9 (20%) developed resistance but were subsequently placed into remission with cisplatin-based chemotherapy, and 4 (9%) died of widespread metastatic disease. Clinical complete response to EMA-CO was significantly influenced by duration of disease from antecedent pregnancy to treatment (<6 months, 84%, vs >6 months, 43%), metastatic site (lung and pelvis, 73%, vs other, 40%), and WHO score (< or =7, 96%, vs >7, 36%). The EMA-CO chemotherapy regimen produced no life-threatening toxicity, caused grade 3-4 hematologic toxicity in 1.6% of cycles, and was associated with neutropenia necessitating a 1-week delay in treatment in only 13.5% of cycles.

Conclusion: EMA-CO chemotherapy is a well-tolerated and highly effective treatment for high-risk gestational trophoblastic neoplasia, yielding a 71% complete response rate and a 91% survival rate in this series.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dactinomycin / administration & dosage
  • Dactinomycin / adverse effects
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Gestational Trophoblastic Disease / drug therapy*
  • Humans
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Vincristine / administration & dosage
  • Vincristine / adverse effects


  • Dactinomycin
  • Vincristine
  • Etoposide
  • Cyclophosphamide
  • Methotrexate

Supplementary concepts

  • EMA-CO protocol