This phase I trial is studying the side effects and best way to give radiation therapy when given together with topotecan and cisplatin in treating patients with locally advanced cervical cancer. This trial is also studying the best dose of topotecan when given in this regimen. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as topotecan and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of pelvic radiotherapy, cisplatin, and topotecan in patients with locally advanced cervical cancer.

II. Determine the maximum tolerated dose (MTD) of topotecan when administered in this regimen in this patient population.

SECONDARY OBJECTIVES:

I. Determine the site of recurrence (local vs distant) in patients treated with this regimen.

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

Patients undergo radiotherapy 5 days a week for 6 weeks. Patients receive cisplatin IV and topotecan IV over 30 minutes once weekly for a total of 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 6 patients experiences dose-limiting toxicity. Once the MTD is determined, an additional cohort of 20 patients receives treatment as above at the MTD.

After completion of study treatment, patients are followed periodically for 5 years.

Inclusion Criteria:

• Histologically confirmed primary invasive carcinoma of the uterine cervix

  • Stages IB2, II, IIIB, and IVA disease
  • Any cell type

• No known metastasis to scalene nodes or organs outside the radiation field

• No known intraperitoneal metastases

• No evidence of extrapelvic disease based on negative CT or PET scan

• Must enroll within 8 weeks of diagnosis

• Performance status - GOG 0-2

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• SGOT ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Creatinine normal

• Creatinine clearance > 50 mL/min

• Prior ureteral obstruction allowed provided stent or nephrostomy tube has been placed

• No renal abnormalities, such as pelvic kidney, horseshoe kidney, or prior renal transplantation that would require modification of radiation fields

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other malignancy within the past 5 years except nonmelanoma skin cancer

• No septicemia or severe infection

• No other medical or psychiatric condition that would preclude study compliance

• No prior chemotherapy for any prior malignancy

• No prior cytotoxic chemotherapy for this malignancy

• No prior radiotherapy for any prior malignancy

• No prior pelvic or abdominal radiotherapy for this malignancy

• No prior therapy for this malignancy