Phase III Trial of Weekly Methotrexate or Pulsed Dactinomycin for Low-Risk Gestational Trophoblastic Neoplasia: A Gynecologic Oncology Group Study
Uterus “Gestational Trophoblastic Neoplasia (GTN)“
The best regimen for the primary treatment of low-risk GTN
Type of study
Phase III Randomized Clinical trial
Weekly Parenteral Methotrexate vs. Biweekly Pulsed Dactinomycin
Experimental arm (Intervention)
Biweekly Dactinomycin 1.25 mg/m2 (IV)
Weekly Methotrexate 30 mg/m2 (IM)
Complete Response (CR), determined by a normal BhCG sustained over four weekly measurements
- Toxicity of each regimen
- Recurrence rate
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.
- Did not meet criteria for persistence
- WHO risk score > 6
- Ineligible cell types
- Inadequate documentation of disease
|Total number (n0)||120||120|
|Complete response (%)||69.7%||53.3%|
|No response (%)||26.6%||44.9%|
|Not evaluable for response (%)||3.7%||1.9%|
- 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.
The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN
- 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).