Advertisement

EMA vs EMACO in the treatment of gestational trophoblastic neoplasia

  • Nida Jareemit
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
    Search for articles by this author
  • Neil S. Horowitz
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

    Dana-Farber Cancer Institute, Boston, MA, United States

    New England Trophoblastic Disease Center, Boston, MA, United States
    Search for articles by this author
  • Donald P. Goldstein
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

    Dana-Farber Cancer Institute, Boston, MA, United States

    New England Trophoblastic Disease Center, Boston, MA, United States
    Search for articles by this author
  • Ross S. Berkowitz
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

    Dana-Farber Cancer Institute, Boston, MA, United States

    New England Trophoblastic Disease Center, Boston, MA, United States
    Search for articles by this author
  • Kevin M. Elias
    Correspondence
    Corresponding author at: Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02215, United States.
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

    Dana-Farber Cancer Institute, Boston, MA, United States

    New England Trophoblastic Disease Center, Boston, MA, United States
    Search for articles by this author

      Highlights

      • In multivariate analysis, EMA had similar efficacy to EMACO for the treatment of GTN.
      • Time to remission for EMA and EMACO was similar.
      • Patients receiving EMA experienced greater toxicity, but this likely stemmed from lower rates of growth factor support.

      Abstract

      Objective

      To compare experiences with EMA versus EMACO in the treatment of gestational trophoblastic neoplasia.

      Methods

      The medical records of women diagnosed with GTN at the New England Trophoblastic Disease Center from 1986 to 2019 were reviewed, and women receiving EMA or EMACO as their first multiagent regimen were eligible. Clinical characteristics, treatment, outcomes, and adverse events were compared between the two groups.

      Results

      We identified 44 and 39 patients who received EMA and EMACO, respectively. The complete remission rate was significantly higher in the EMA group (97.7%) than in the EMACO group (71.8%) (p = 0.001). However, patients receiving EMACO were more likely to have adverse prognostic factors such as higher median prognostic risk score (8 vs 4, p < 0.001), non-molar antecedent pregnancy (59 vs 27.3%, p = 0.014) and distant metastasis (64.1 vs 47.7%, p = 0.017). Time to complete remission was also similar (p = 0.947) with a median of 12 weeks with EMA and 13.1 weeks with EMACO. There was no significant difference in treatment delays or use of adjuvant surgery. After multivariate analysis, chemotherapy regimen (EMA or EMACO) did not retain prognostic significance for remission. Overall toxicities were more frequent in EMA (60.2 vs 32.7%, p < 0.001), especially neutropenia, but this did not delay treatment and likely resulted from less growth factor support (18.2 vs 48.7%, p = 0.003).

      Conclusions

      When controlling for other prognostic factors, outcomes with EMA appear similar to EMACO. It may be worthwhile to investigate whether EMA, a simpler and less costly regimen, may be as effective as EMACO in the treatment of GTN.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Gynecologic Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ngan S.
        • Seckl M.J.
        Gestational trophoblastic neoplasia management: an update.
        Curr. Opin. Oncol. 2007; 19: 486-491
        • Brinton L.A.
        • Bracken M.B.
        • Connelly R.R.
        Choriocarcinoma incidence in the United States.
        Am. J. Epidemiol. 1986; 123: 1094-1100
        • Berkowitz R.S.
        • Goldstein D.P.
        Current management of gestational trophoblastic diseases.
        Gynecol. Oncol. 2009; 112: 654-662
        • Ngan H.Y.S.
        • Seckl M.J.
        • Berkowitz R.S.
        • Xiang Y.
        • Golfier F.
        • Sekharan P.K.
        • et al.
        Update on the diagnosis and management of gestational trophoblastic disease.
        Int. J. Gynaecol. Obstet. 2018; 143: 79-85
        • Kohorn E.I.
        The new FIGO 2000 staging and risk factor scoring system for gestational trophoblastic disease: description and critical assessment.
        Int. J. Gynecol. Cancer. 2001; 11: 73-77
        • Hammond C.B.
        • Borchert L.G.
        • Tyrey L.
        • Creasman W.T.
        • Parker R.T.
        Treatment of metastatic trophoblastic disease: good and poor prognosis.
        Am. J. Obstet. Gynecol. 1973; 115: 451-457
        • Bagshawe K.D.
        Risk and prognostic factors in trophoblastic neoplasia.
        Cancer. 1976; 38: 1373-1385
        • Brewer J.I.
        • Eckman T.R.
        • Dolkart R.E.
        • Torok E.E.
        • Webster A.
        Gestational trophoblastic disease. A comparative study of the results of therapy in patients with invasive mole and with choriocarcinoma.
        Am. J. Obstet. Gynecol. 1971; 109: 335-340
        • Berkowitz R.S.
        • Goldstein D.P.
        • Horowitz N.S.
        Initital management of high-risk gestational trophoblastic neoplasia.
        in: Goff B. Dizon D.S. UptoDate. Wolters Kluwer, 2019 (November 12)
        • Escobar P.F.
        • Lurain J.R.
        • Singh D.K.
        • Bozorgi K.
        • Fishman D.A.
        Treatment of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy.
        Gynecol. Oncol. 2003; 91: 552-557
        • Turan T.
        • Karacay O.
        • Tulunay G.
        • Boran N.
        • Koc S.
        • Bozok S.
        • et al.
        Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia.
        Int. J. Gynecol. Cancer. 2006; 16: 1432-1438
        • Lu W.G.
        • Ye F.
        • Shen Y.M.
        • Fu Y.F.
        • Chen H.Z.
        • Wan X.Y.
        • et al.
        EMA-CO chemotherapy for high-risk gestational trophoblastic neoplasia: a clinical analysis of 54 patients.
        Int. J. Gynecol. Cancer. 2008; 18: 357-362
        • Cagayan M.S.
        High-risk metastatic gestational trophoblastic neoplasia. Primary management with EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) chemotherapy.
        J. Reprod. Med. 2012; 57: 231-236
        • Lurain J.R.
        • Singh D.K.
        • Schink J.C.
        Primary treatment of metastatic high-risk gestational trophoblastic neoplasia with EMA-CO chemotherapy.
        J. Reprod. Med. 2006; 51: 767-772
        • Lurain J.R.
        • Singh D.K.
        • Schink J.C.
        Management of metastatic high-risk gestational trophoblastic neoplasia: FIGO stages II-IV: risk factor score > or = 7.
        J. Reprod. Med. 2010; 55: 199-207
        • Alifrangis C.
        • Agarwal R.
        • Short D.
        • Fisher R.A.
        • Sebire N.J.
        • Harvey R.
        • et al.
        EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis.
        J. Clin. Oncol. 2013; 31: 280-286
        • Soto-Wright V.
        • Goldstein D.P.
        • Bernstein M.R.
        • Berkowitz R.S.
        The management of gestational trophoblastic tumors with etoposide, methotrexate, and actinomycin D.
        Gynecol. Oncol. 1997; 64: 156-159
        • Matsui H.
        • Suzuka K.
        • Iitsuka Y.
        • Seki K.
        • Sekiya S.
        Combination chemotherapy with methotrexate, etoposide, and actinomycin D for high-risk gestational trophoblastic tumors.
        Gynecol. Oncol. 2000; 78: 28-31
        • Dobson L.S.
        • Lorigan P.C.
        • Coleman R.E.
        • Hancock B.W.
        Persistent gestational trophoblastic disease: results of MEA (methotrexate, etoposide and dactinomycin) as first-line chemotherapy in high risk disease and EA (etoposide and dactinomycin) as second-line therapy for low risk disease.
        Br. J. Cancer. 2000; 82: 1547-1552
        • Byun S.W.
        • Park T.C.
        • Bae S.N.
        Conservative chemotherapy in gestational trophoblastic disease: experience with etoposide, methotrexate, and dactinomycin chemotherapy.
        Int. J. Gynecol. Cancer. 2016; 26: 790-795
        • Agarwal R.
        • Alifrangis C.
        • Everard J.
        • Savage P.M.
        • Short D.
        • Tidy J.
        • et al.
        Management and survival of patients with FIGO high-risk gestational trophoblastic neoplasia: the U.K. experience, 1995–2010.
        J. Reprod. Med. 2014; 59: 7-12
        • Newlands E.S.
        • Bagshawe K.D.
        Anti-tumour activity of the epipodophyllin derivative VP16-213 (etoposide: NSC-141540) in gestational choriocarcinoma.
        Eur. J. Cancer. 1980; 16: 401-405
        • Newlands E.S.
        • Bagshawe K.D.
        The role of VP16-213 (etoposide; NSC-141540) in gestational choriocarcinoma.
        Cancer Chemother. Pharmacol. 1982; 7: 211-214
        • Newlands E.S.
        • Bagshawe K.D.
        • Begent R.H.
        • Rustin G.J.
        • Holden L.
        • Dent J.
        Developments in chemotherapy for medium- and high-risk patients with gestational trophoblastic tumours (1979–1984).
        Br. J. Obstet. Gynaecol. 1986; 93: 63-69
        • Newlands E.S.
        • Bagshawe K.D.
        • Begent R.H.
        • Rustin G.J.
        • Holden L.
        Results with the EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) regimen in high risk gestational trophoblastic tumours, 1979 to 1989.
        Br. J. Obstet. Gynaecol. 1991; 98: 550-557
        • Kim S.J.
        • Bae S.N.
        • Kim J.H.
        • Kim C.T.
        • Han K.T.
        • Lee J.M.
        • et al.
        Effects of multiagent chemotherapy and independent risk factors in the treatment of high-risk GTT −25 years experiences of KRI-TRD.
        Int. J. Gynaecol. Obstet. 1998; 60: S85-S96
        • Deng L.
        • Zhang J.
        • Wu T.
        • Lawrie T.A.
        Combination chemotherapy for primary treatment of high-risk gestational trophoblastic tumour.
        Cochrane Database Syst. Rev. 2013; (CD005196): 1
        • Cui W.
        • Stern C.
        • Hickey M.
        • Goldblatt F.
        • Anazodo A.
        • Stevenson W.S.
        • et al.
        Preventing ovarian failure associated with chemotherapy.
        Med. J. Aust. 2018; 209: 412-416
        • Sklar C.A.
        • Mertens A.C.
        • Mitby P.
        • Whitton J.
        • Stovall M.
        • Kasper C.
        • et al.
        Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study.
        J. Natl. Cancer Inst. 2006; 98: 890-896
        • Balachandran K.
        • Salawu A.
        • Ghorani E.
        • Kaur B.
        • Sebire N.J.
        • Short D.
        • et al.
        When to stop human chorionic gonadotrophin (hCG) surveillance after treatment with chemotherapy for gestational trophoblastic neoplasia (GTN): a national analysis on over 4,000 patients.
        Gynecol. Oncol. 2019; 155: 8-12