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)“
Pubmed link
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