Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study

J Clin Oncol. 2011 Mar 1;29(7):825-31. doi: 10.1200/JCO.2010.30.4386. Epub 2011 Jan 24.

Abstract

Purpose: There is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia (GTN).

Patients and methods: Two commonly used single-drug regimens were compared with respect to the proportion of patients meeting the criteria for a complete response (CR) in a randomized phase III trial conducted by the Gynecologic Oncology Group. Eligibility was purposefully broad to maximize the generalizability of the results and included patients with a WHO risk score of 0 to 6 and patients with metastatic disease (limited to lung lesions < 2 cm, adnexa, or vagina) or choriocarcinoma.

Results: Two hundred forty women were enrolled, and 216 were deemed eligible. Biweekly intravenous dactinomycin 1.25 mg/m² was statistically superior to weekly intramuscular (IM) methotrexate 30 mg/m² (CR: 70% v 53%; P = .01). Similarly, in patients with low-risk GTN as defined before the 2002 WHO risk score revisions (risk score of 0 to 4 and excluding choriocarcinoma), response was 58% and 73% in the methotrexate and dactinomycin arms, respectively (P = .03). Both regimens were less effective if the WHO risk score was 5 or 6 or if the diagnosis was choriocarcinoma (CR: 9% and 42%, respectively). There were two potential recurrences; one at 4 months (dactinomycin) and one at 22 months (methotrexate). Not all patients completed follow-up. Both regimens were well tolerated.

Conclusion: The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN, a generally curable disease.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biopsy, Needle
  • Choriocarcinoma / drug therapy
  • Choriocarcinoma / pathology
  • Dactinomycin / administration & dosage*
  • Dactinomycin / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Gestational Trophoblastic Disease / drug therapy*
  • Gestational Trophoblastic Disease / pathology*
  • Humans
  • Immunohistochemistry
  • Injections, Intramuscular
  • Injections, Intravenous
  • Logistic Models
  • Maximum Tolerated Dose
  • Medical Oncology
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Neoplasm Staging
  • Odds Ratio
  • Ontario
  • Pregnancy
  • Pulse Therapy, Drug
  • Treatment Outcome
  • Young Adult

Substances

  • Dactinomycin
  • Methotrexate