Radiation Therapy With or Without Chemotherapy in Treating Patients With High-Risk Endometrial Cancer

OBJECTIVES:

• Compare relapse-free survival of patients with high-risk endometrial carcinoma treated in the adjuvant setting with either radiotherapy alone or radiotherapy and chemotherapy given sequentially.
• Compare overall survival of this patient population treated with these 2 adjuvant regimens.
• Evaluate the addition of chemotherapy to standard adjuvant radiotherapy, in terms of toxicity, in these patients.
• Study whether the pattern of relapse in these patients is influenced by the addition of chemotherapy to adjuvant radiotherapy.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to center and histologic type (serous papillary and clear cell vs all other types). Patients are randomized to 1 of 2 treatment arms.

All patients undergo hysterectomy with bilateral salpingooophorectomy and extirpation of macroscopic suspicious lymph nodes.

• Arm I: Within 7 weeks after surgery, patients begin radiotherapy.
• Arm II: Patients receive radiotherapy followed by or preceded by chemotherapy*. Patients receive cisplatin IV over 60 minutes and doxorubicin or epirubicin IV over 10-20 minutes on day 1. Treament repeats every 21 days for 4 courses.

NOTE: *If radiotherapy is preceded by chemotherapy, radiotherapy begins within 4 weeks after chemotherapy.

Patients are followed at 3 and 6 months and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 400 patients (200 per treatment arm) will be accrued for this study within 5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed endometrial cancer of 1 of the following types:

• Clear cell carcinoma
• Serous papillary carcinoma
• Undifferentiated (anaplastic) carcinoma
• Poorly differentiated (FIGO grade 3) adenocarcinoma with infiltration to more than half the myometrial thickness
• No small cell carcinoma with neuroendocrine differentiation
• Primary in FIGO surgical stage I or occult stage II
• No spread of disease outside the uterine corpus except to pelvic lymph nodes

• No spread of disease to para-aortic lymph nodes
• Positive peritoneal washings allowed
• No preoperative macroscopic tumor involvement of the cervix

• Microscopic tumor involvement of the cervix on histopathological evaluation of the operative uterine specimen allowed

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Adequate bone marrow function
• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Adequate hepatic function

Renal:

• Adequate renal function
• Creatinine no greater than 1.4 mg/dL

Pulmonary:

• Adequate pulmonary function

Other:

• Not pregnant or nursing
• Fit to receive combination chemotherapy
• No other malignancy except basal cell or squamous cell skin cancer
• No uncontrolled or potentially active site of infection (e.g., fistula or abscesses)
• No other concurrent condition that would produce a substantial increase in risk for complications from radiotherapy
• No other concurrent condition that would interfere with adequate follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior preoperative irradiation

Surgery:

• No prior extensive abdominal surgery