Radiation Therapy, Paclitaxel, and Cisplatin in Treating Patients With Cancer of the Cervix

OBJECTIVES:

• Determine the toxicity of extended field radiotherapy with concurrent paclitaxel and cisplatin chemotherapy (as radiation sensitization) in patients with previously untreated carcinoma of the cervix metastatic to the para-aortic lymph nodes.
• Determine the maximum tolerated dose of paclitaxel when combined with cisplatin plus extended field radiotherapy in this patient population.
• Determine the effect of this treatment regimen on progression-free survival, overall survival, and site of recurrence (local vs distant) in these patients.

OUTLINE: This is a multicenter, dose-escalation study of paclitaxel.

Patients receive external beam radiotherapy (RT) to the para-aortic nodes and the pelvis daily for 5 weeks; RT must be completed within 8 weeks of its initiation. During or after external beam RT, intracavitary radiation is administered 1-5 times. Concurrently with external beam RT, patients receive paclitaxel IV over 1 hour followed immediately by cisplatin IV on days 1, 8, 15, 22, 29, and 36.

Cohorts of 3-6 patients receive escalating doses of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter or until the time of recurrence or death.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Histologically proven previously untreated invasive carcinoma of the uterine cervix

• Squamous cell carcinoma
• Adenosquamous carcinoma
• Adenocarcinoma
• TNM classification stage IIIB or IVA (FIGO classification stage IB, IIA, IIB, IIIA, IIIB, or IVA)
• Cytologically or histologically proven metastases to the para-aortic lymph nodes
• No more than 8 weeks since diagnosis
• No metastases to scalene nodes, intraperitoneal metastases, or metastases to other organs outside the radiation field at the time of original clinical and surgical staging

• Negative CT scan of the chest
• Patients with ureteral obstruction must be treated with stent or nephrostomy tube

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• GOG 0-2

Life expectancy:

• At least 6 months

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 times normal
• SGOT no greater than 3 times normal

Renal:

• Creatinine less than 2.0 mg/dL
• No renal abnormalities (e.g., pelvic kidney, horseshoe kidney, or renal transplantation) requiring modification of radiation fields

Other:

• Not pregnant
• No septicemia or severe infection
• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior cytotoxic chemotherapy for this or other malignancy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for this or other malignancy
• No prior radiotherapy to pelvis or abdomen

Surgery:

• Not specified

Other:

• No other prior therapy for this malignancy