A Phase III Trial of Postoperative Chemotherapy or no Further Treatment for Patients With Node-negative Stage I-II Intermediate or High Risk Endometrial Cancer
Patients with medium and high risk stage I and II endometrial cancers have, despite radical
surgery, a rather high risk for progression.
Adjuvant radiotherapy was the traditional therapy for many decades. Four randomized phase
III studies and a meta-analysis have revealed that adjuvant radiotherapy improves local
control at the cost of excessive short and long term toxicity, though has absolutely no
impact on survival.
Two phase III studies have randomized between adjuvant radiotherapy versus adjuvant
chemotherapy, both failed to show any difference in survival between radiotherapy and
chemotherapy, though both studies are criticized for inferior chemotherapy regimens or
inclusion of good prognosis patients. The GOG-122 study on more advanced cases (stage 3 & 4)
randomized between combination chemotherapy versus whole abdominal irradiation and found
significant improvement in survival in the chemotherapy arm.
NSGO-EC-9501 and MaNGO studies have indicated that adjuvant chemotherapy added to adjuvant
radiotherapy may improve survival compared to adjuvant radiotherapy alone in early stage
medium and high risk patients. One may conclude that impact on survival comes only from
chemotherapy. Many investigators have therefore adapted adjuvant chemotherapy as standard
treatment in various countries including Denmark. However, such conclusion has low level of
evidence, as there are no randomized phase III studies comparing postoperative observation
alone versus adjuvant chemotherapy.
It is of utmost importance to demonstrate efficacy of adjuvant combination chemotherapy in a
randomized phase III trial comparing to no further treatment in the medium and high risk
node negative stage 1 & 2 patients.
Combination chemotherapy regimen of paclitaxel-carboplatin is proposed in this study, as
this combination is effective and well tolerated.
The eligible patients for such a study are a fraction of patients with endometrial cancer
therefore this study will be performed within the ENGOT collaboration.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To detect an overall absolute difference in five-year survival of 10%, from 72% to 82%, at the 2.5% level with 80% power, 135 deaths corresponding to 644 patients are needed. Assuming a dropout rate of 5%, 678 patients have to be accrued, leaving 644 patients for the overall analysis.
Mansoor R Mirza, MD
Danish Gynecological Cancer Group
DKMA: The Danish Medicines Agency