Comparison of Two Combination Chemotherapy Regimens Plus Radiation Therapy in Treating Patients With Stage III or Stage IV Endometrial Cancer

OBJECTIVES:

I. Compare survival and progression-free survival in patients with stage III endometrial carcinoma treated with tumor volume-directed pelvic radiotherapy with or without paraaortic radiotherapy followed by cisplatin and doxorubicin with or without paclitaxel.

II. Compare short and long-term toxic effects of these treatment regimens in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to radiotherapy field (pelvic vs extended field). Within 8 weeks after surgery, patients receive tumor volume-directed pelvic radiotherapy with or without paraaortic nodal radiotherapy once daily for 5 consecutive days for up to 16 weeks after surgery. Within 8 weeks of completing radiotherapy, patients are randomized to 1 of 2 chemotherapy treatment arms.

Arm I: Patients receive doxorubicin IV over 30 minutes immediately followed by cisplatin IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or pegfilgrastim on days 2-11.

Arm II: Patients receive doxorubicin and cisplatin as in arm I, paclitaxel IV over 3 hours on day 2, and G-CSF SC or pegfilgrastim on days 3-12. Treatment repeats every 3 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 614 patients (307 per treatment arm) will be accrued for this study within 5.2 years.

Inclusion criteria

• Histologically confirmed advanced endometrial carcinoma with any histology, including:

• Clear cell and serous papillary carcinoma
• Surgical stage III disease, including:

• Positive adnexa
• Tumor invading the serosa
• Positive pelvic and/or paraaortic nodes
• Involvement of bowel mucosa
• Intraabdominal metastases
• Positive pelvic washings
• Vaginal involvement within the radiation port
• Must have had prior surgery, including hysterectomy and bilateral salpingo-oophorectomy

• Tumor maximally debulked to a maximum residual diameter of no greater than 2 cm
• Paraaortic lymph node sampling allowed

• If positive, must have negative chest CT scan
• No recurrent disease
• No parenchymal liver metastases
• No disease outside the abdomen
• Performance status - GOG 0-2
• At least 3 months
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times normal
• SGOT/SGPT no greater than 3 times normal
• Alkaline phosphatase no greater than 3 times normal
• Creatinine no greater than 1.6 mg/dL
• LVEF at least 50% within 6 months of study entry
• No other prior or concurrent malignancy within the past 5 years except adequately treated nonmelanoma skin cancer
• No serious comorbid illness that would preclude study participation
• No prior chemotherapy
• See Disease Characteristics
• No prior pelvic or abdominal radiotherapy
• No prior radiotherapy for prior malignancy
• See Disease Characteristics