• Overall survival at 5 years [ Designated as safety issue: No ]
  
• Failure-free survival at 5 years [ Designated as safety issue: No ]
  

• Quality of life by QLQ-C30 v3.0 [ Designated as safety issue: No ]
  
• Severe treatment-related morbidity [ Designated as safety issue: No ]
  
• Rate of vaginal or pelvic relapse [ Designated as safety issue: No ]
  
• Rate of distant metastases [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the overall survival and failure-free survival of patients with high-risk stage IB-III endometrial carcinoma treated with concurrent chemoradiotherapy followed by adjuvant chemotherapy vs pelvic radiotherapy alone.

Secondary

• Compare the rates of pelvic and distant recurrence, severe (grades 3 and 4) treatment-related toxicity, and quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter, prospective, open-label, randomized, controlled study. Patients are stratified according to participating group (Dutch Cooperative Gynecologic Oncology Group vs United Kingdom National Cancer Research Institute), type of surgery (total abdominal hysterectomy and bilateral salpingo-oophorectomy [TAH-BSO] vs TAH-BSO plus lymphadenectomy vs laparoscopically-assisted vaginal hysterectomy), stage (IB vs IC vs II vs III), and histological type (endometrioid carcinoma vs serous or clear cell carcinoma). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cisplatin IV over 1-2 hours on days 1 and 22 and external-beam pelvic radiotherapy 5 days a week for up to 6 weeks. At least 3 weeks after completion of chemoradiotherapy, patients undergo adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Adjuvant chemotherapy repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo external-beam pelvic radiotherapy as in arm I. In both arms, patients with cervical involvement undergo vaginal brachytherapy.

Quality of life is assessed at baseline, completion of radiotherapy, completion of chemotherapy, at 6 months, and then once a year for 5 years.

After completion of study therapy, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed endometrial carcinoma meeting ≥ 1 of the following criteria:

  • Stage IB grade 3 disease with documented lymph-vascular space invasion
  • Stage IC grade 3 disease
  • Stage IIA grade 3 disease
  • Stage IIB any grade disease

  • Stage IIIA or IIIC disease

    • Stage IIIA disease based on peritoneal cytology alone allowed if disease is grade 3
  • Stage IB-III disease with serous or clear cell histology

• Must have undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy within the past 4-8 weeks

  • Lymphadenectomy and/or full surgical staging allowed

  • No residual macroscopic tumor after surgery

    • No macroscopic stage IIB disease with prior radical (Wertheim type) hysterectomy
• No uterine sarcoma

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• WBC ≥ 3,000/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine clearance > 60 mL/min (calculated according to Cockroft) or > 50 mL/min (EDTA clearance or measured creatinine clearance)
• No prior malignancy within the past 10 years except for basal cell carcinoma of the skin
• No prior diagnosis of Crohn's disease or ulcerative colitis
• No impaired cardiac function that would prohibit the infusion of large amounts of fluid
• No peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior pelvic radiotherapy
• No prior hormonal therapy or chemotherapy for this tumor