Epoetin Beta in Treating Anemia in Patients With Cervical Cancer

OBJECTIVES:

• Compare the effectiveness of epoetin beta vs standard care for anemia management, in terms of increased hemoglobin levels and the correlation with reduced relapse/treatment failure rate, in patients with stage IIB, III, or IVA cervical cancer treated with cisplatin and radiotherapy.
• Compare the safety of these regimens in these patients.
• Compare the relapse-free and overall survival of patients treated with these regimens.
• Compare the frequency and localization of relapses and metastases in patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.
• Compare the type, frequency, and degree of adverse events in patients treated with these regimens.
• Compare the overall response rate in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, parallel-group, multicenter study. Patients are stratified according to country, disease stage, and brachytherapy technique. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy 5 days a week for 6 weeks. Patients also undergo high-dose rate, low-dose rate, or boost brachytherapy. Patients receive cisplatin IV beginning on day 1 of radiotherapy and continuing weekly for 6 weeks. Patients also receive epoetin beta subcutaneously 3 times a week beginning 2 weeks before radiotherapy and continuing for 8 weeks.
• Arm II: Patients undergo radiotherapy and brachytherapy and receive cisplatin as in arm I.

Quality of life is assessed at baseline, after the last treatment, and at 3 months.

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

PROJECTED ACCRUAL: A total of 80-450 patients will be accrued for this study within 4-22.5 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IIB, III, or IVA cervical cancer

• No chorion carcinoma or neuroendocrine small cell carcinoma
• Previously untreated disease
• Must be scheduled to undergo radiotherapy and receive cisplatin as primary therapy
• Hemoglobin 8.0-13.0 g/dL
• No relevant acute bleeding within the past 3 months, including anemia caused by gross bleeding from tumor
• No distant metastasis
• No positive para-aortic lymph nodes

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• WHO 0-2

Life expectancy

• At least 3 months

Hematopoietic

• See Disease Characteristics
• WBC greater than 3,000/mm3
• Platelet count greater than 100,000/mm3
• No hemolytic anemia
• No transferrin saturation less than 20% that cannot be treated with IV iron
• No hemoglobinopathies (i.e., sickle cell disease or thalassemia of all types)

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Transaminases no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine clearance greater than 60 mL/min

Cardiovascular

• No chronic heart failure
• No New York Heart Association class II-IV heart disease
• No uncontrolled arterial hypertension (systolic blood pressure at least 170 mmHg, diastolic blood pressure at least 100 mmHg)
• No prior deep vein thrombosis
• No thrombocytosis

Other

• No vitamin B12 deficiency
• No folic acid deficiency
• No newly diagnosed (unstable) epilepsy
• No acute infection
• No other malignancy within the past 5 years except basal cell carcinoma in situ
• No known peripheral neuropathy or moto-sensory neurotoxicity grade 2 or greater
• No impaired hearing grade 2 or greater
• No hypersensitivity to benzyl alcohol, benzoic acid, benzalkonium chloride, or any excipients of cisplatin preparations
• Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 months since prior epoetins or related compounds

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy for cervical cancer

Surgery

• Not specified

Other

• At least 30 days since prior investigational drugs
• No prior systemic antineoplastic therapy for cervical cancer
• No other concurrent investigational drugs