Radiation Therapy Plus Celecoxib, Fluorouracil, and Cisplatin in Patients With Locally Advanced Cervical Cancer

OBJECTIVES:

• Determine treatment-related toxicity rates in patients with locally advanced cervical cancer treated with external beam radiotherapy and brachytherapy concurrently with celecoxib, fluorouracil, and cisplatin.
• Determine whether this regimen increases locoregional control rates, distant control, disease-free survival, and overall survival in these patients.
• Determine whether first-failure patterns in patients treated with this regimen are changed compared to historical controls.

OUTLINE: This is a multicenter study.

Patients undergo external beam pelvic radiotherapy once daily five days a weeks for 5 weeks beginning on day 1. Within 8 weeks, patients undergo low-dose or high-dose brachytherapy. Patients also receive concurrent chemotherapy comprising fluorouracil IV continuously over days 2-5, 23-26, and 44-47 and cisplatin IV over 4 hours on days 1, 22, and 43. Oral celecoxib is administered twice daily beginning on day 1 and continuing for 12 months.

Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 1.5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous, adenocarcinoma, or adenosquamous carcinoma of the cervix

• Stage IIB-IVA OR
• Stage IB-IIA with pelvic node metastases and/or tumor size at least 5 cm
• No small cell, carcinoid, glassy cell, clear cell, or adenoid cystic disease
• No metastatic disease outside of pelvis
• No para-aortic disease

PATIENT CHARACTERISTICS:

Age:

• 18 to 85

Performance status:

• Zubrod 0-2

Life expectancy:

• At least 6 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST or ALT no greater than 2.5 times upper limit of normal (ULN)

Renal:

• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 50 mL/min
• Calcium no greater than 1.3 times ULN

Cardiovascular:

• No severe heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• HIV negative
• No prior allergy to sulfonamides or non-steroidal anti-inflammatory drugs (NSAIDs)
• No prior hypersensitivity to celecoxib or any component of its formulation
• No medical or psychiatric illness that would preclude study
• No active gastrointestinal (GI) ulcer, GI bleeding, or inflammatory bowel disease
• No other prior malignancy within the past 5 years except cutaneous basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No recent prior celecoxib or other cyclo-oxygenase-2 inhibitor

Chemotherapy:

• No prior systemic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to pelvis except transvaginal radiotherapy to control bleeding

Surgery:

• No prior surgery for cervical cancer except biopsy

Other:

• No concurrent phenytoin or lithium
• No other concurrent NSAIDs