Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study.
OBJECTIVE
To establish an optimal adjuvant therapy for intermediate- and high-risk endometrial cancer patients, we conducted a multi-center randomized phase III trial of adjuvant pelvic radiation therapy (PRT) versus cyclophosphamide-doxorubicin-cisplatin (CAP) chemotherapy in women with endometrioid adenocarcinoma with deeper than 50% myometrial invasion.


METHODS
Among 385 evaluated patients, 193 patients received PRT and 192 received CAP. The PRT group received at least 40 Gy. The CAP group received cyclophosphamide (333 mg/m2), doxorubicin (40 mg/m2) and cisplatin (50 mg/m2) every 4 weeks for 3 or more courses.


RESULTS
No statistically significant differences in progression-free survival (PFS) and overall survival (OS) were observed. The 5-year PFS rates in the PRT and CAP groups were 83.5% and 81.8% respectively, while the 5-year OS rates were 85.3% and 86.7% respectively. These rates were also not significantly different in a low- to intermediate-risk group defined as stage IC patients under 70 years old with G1/2 endometrioid adenocarcinoma. However, among 120 patients in a high- to intermediate-risk group defined as (1) stage IC in patients over 70 years old or with G3 endometrioid adenocarcinoma or (2) stage II or IIIA (positive cytology), the CAP group had a significantly higher PFS rate (83.8% vs. 66.2%, log-rank test P=0.024, hazard ratio 0.44) and higher OS rate (89.7% vs. 73.6%, log-rank test P=0.006, hazard ratio 0.24). Adverse effects were not significantly increased in the CAP group versus the PRT group.


CONCLUSIONS
Adjuvant chemotherapy may be a useful alternative to radiotherapy for intermediate-risk endometrial cancer.
Susumu
Nobuyuki
N
School of Medicine, Keio University, Shinjyuku-ku, Tokyo, Japan.
Sagae
Satoru
S
Udagawa
Yasuhiro
Y
Niwa
Kenji
K
Kuramoto
Hiroyuki
H
Satoh
Shinji
S
Kudo
Ryuichi
R
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D010349:Patient Compliance; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D016896:Treatment Outcome
D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin