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Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia
  1. Catherine Prouvot, MD*,
  2. François Golfier, MD, PhD*,,
  3. Jérôme Massardier, MD,,
  4. Benoit You, MD, PhD,§,
  5. Jean-Pierre Lotz, MD, PhD,
  6. Sophie Patrier, MD,
  7. Mojgan Devouassoux, MD, PhD#,
  8. Anne-Marie Schott, MD, PhD,**,
  9. Touria Hajri, MSc and
  10. Pierre-Adrien Bolze, MD*,
  1. * Department of Gynecological Surgery and Oncology, Obstetrics, University Hospital Lyon Sud, University of Lyon 1;
  2. French Centre for Trophoblastic Diseases, University Hospital Lyon Sud, Pierre Bénite;
  3. Department of Prenatal Diagnosis, University Hospital Femme Mere Enfant, Bron;
  4. § Department of Medical Oncology, University Hospital Lyon Sud, University of Lyon 1, Pierre Bénite;
  5. Department of Medical Oncology, Alliance for Cancer Research, Tenon Hospital, Public Assistance Hospitals of Paris, Paris;
  6. Department of Pathology, University Hospital of Rouen, Rouen;
  7. # Department of Pathology Croix Rousse Hospital, Hospices Civils de Lyon, Claude Bernard University Lyon 1; and
  8. ** Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Lyon, France.
  1. Address correspondence and reprint requests to Pierre-Adrien Bolze, MD, Centre Français des Maladies Trophoblastiques, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, Bâtiment 3B, 2ème étage 69495, Pierre Bénite, France. E-mail: pierre-adrien.bolze{at}chu-lyon.fr.

Abstract

Objective The objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate.

Methods From 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure.

Results A total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3–83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post–dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98–50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%).

Conclusion Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.

  • Gestational trophoblastic neoplasia
  • Dactinomycin
  • Methotrexate
  • Choriocarcinoma
  • Hydatidiform mole

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Footnotes

  • The authors acknowledge the French Ligue Nationale contre le Cancer and the Institut National du Cancer, which have recognized the French Center for Trophoblastic Diseases as a Rare Tumor Center since 2009 and which renewed funding that enabled this study; the French Center for Trophoblastic Diseases thanks all the patients who, by giving their signed consent, allowed for this study to be carried out and all the physicians who declared patients because such nationwide epidemiologic studies directly depend on their constructive collaboration. The authors declare no conflicts of interest.

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