Phase III Trial of Weekly Methotrexate or Pulsed Dactinomycin for Low-Risk Gestational Trophoblastic Neoplasia: A Gynecologic Oncology Group Study

Disease site

Uterus “Gestational Trophoblastic Neoplasia (GTN)

Publication month/year

March 2011

Study question

The best regimen for the primary treatment of low-risk GTN

Type of study

Phase III Randomized Clinical trial

Interventions compared

Weekly Parenteral Methotrexate vs. Biweekly Pulsed Dactinomycin

Experimental arm (Intervention)

Biweekly Dactinomycin 1.25 mg/m2 (IV)

Control arm

Weekly Methotrexate 30 mg/m2 (IM)

Primary outcome

Complete Response (CR), determined by a normal BhCG sustained over four weekly measurements

Secondary outcome
  • Toxicity of each regimen 
  • Recurrence rate
Inclusion criteria
  • FIGO criteria for persistence (1982), one or more of:

    • < 10% decrease in 3 consecutive weekly βhCG values (over 2 weeks)
    • >20% rise in the βhCG value over any two consecutive weekly assays
    • Elevated βhCG level 4 months following initial uterine curettage
    • Metastatic disease in the vagina, parametrium, or lung (if no single lesion exceeded 2 cm radiologically)
    • Histologically proven nonmetastatic choriocarcinoma
  • From 1999 to 2002, If WHO risk score was between 0 and 4.
  • From 2002 to 2007, If WHO risk score was between 0 and 6.
Exclusion criteria
  • Did not meet criteria for persistence
  • WHO risk score > 6
  • Ineligible cell types
  • Inadequate documentation of disease
Results
Dactinomycin Methotrexate
Total number (n0) 120 120
Eligible (n0) 109 107
Complete response (%) 69.7% 53.3%
No response (%) 26.6% 44.9%
Not evaluable for response (%) 3.7% 1.9%
Other results
  • The complete response for patients with a risk score of 0-4 and excluding choriocarcinoma was significantly remarkable for dactinomycin over methotrexate, 73% vs. 58%, respectively.
  • Both regimens are less effective in patients with a risk score of 5-6 or if the diagnosis was choriocarcinoma.
  • Two potential recurrences
    • At 4 months with dactinomycin regimen
    • At 22 months with methotrexate regimen
  • More low-grade GI toxicity among patients receiving dactinomycin, along with rash, alopecia and neutropenia. However, no patient had to have the allocated treatment terminated because of drug-related toxicity.
Conclusions

The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN

Study limitations
  • The study was not designed to test whether the recurrences represented true late ones or were the result of a second consecutive molar gestation.
  • The WHO score was found to have been incorrectly calculated by the registering center in 32% of the patients.
  • The most common error was incorrect scoring of the BhCG level (scientific notation error).
Reviewer name

Bushra Maaqbeh