Doxorubicin and Cisplatin With or Without Paclitaxel in Treating Patients With Locally Advanced, Metastatic, and/or Relapsed Endometrial Cancer

OBJECTIVES:

• Compare the overall survival of patients with locally advanced, metastatic, and/or relapsed endometrial cancer treated with doxorubicin and cisplatin with or without paclitaxel.
• Compare the toxicity of these regimens in these patients.
• Compare the progression-free survival at 18 months of patients treated with these regimens.
• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to performance status (0 vs 1 vs 2), metastatic disease (M0 vs M1), prior pelvic radiotherapy for pelvic recurrence (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive doxorubicin IV over 30 minutes, paclitaxel IV over 3 hours, and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive doxorubicin and cisplatin as in arm I. Quality of life is assessed at baseline, before each course, after courses 3 and 6, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. In the event of progressive disease, quality of life is assessed every 3 months.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. In the event of progressive disease, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed endometrial epithelial carcinoma meeting at least 1 of the following criteria:

• Advanced metastatic and/or relapsed disease
• Locally advanced inoperable or unresectable disease
• No mixed mesodermal tumor and/or tumors showing evidence of sarcomatous elements
• Uterine papillary serous carcinoma allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 10 g/dL (transfusions allowed)

Hepatic

• ALT and AST less than 2 times upper limit of normal (ULN)
• Alkaline phosphatase less than 2 times ULN
• Bilirubin less than 1.5 times ULN

Renal

• Creatinine less than 1.5 times ULN
• Creatinine clearance greater than 50 mL/min

Cardiovascular

• Normal baseline EKG
• Normal baseline LVEF on MUGA or echocardiogram for patients who received prior anthracyclines

Other

• Able to tolerate high-dose dexamethasone
• Must be considered fit for chemotherapy
• No uncontrolled infection
• No other malignancy within the past 5 years except successfully treated basal cell skin cancer or carcinoma in situ of the cervix
• No prior nervous or psychiatric disorder that would preclude study compliance
• No psychological, familial, sociological, or geographic condition that would preclude study participation
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 12 months since prior adjuvant chemotherapy
• Total dose of prior doxorubicin no greater than 200 mg/m^2
• Total dose of prior epirubicin no greater than 300 mg/m^2

Endocrine therapy

• At least 28 days since prior hormonal therapy for patients with partial or complete response after first-line treatment

Radiotherapy

• No prior radiotherapy to any area other than pelvis
• No concurrent radiotherapy

Surgery

• Not specified

Other

• No other concurrent anticancer medications