Comparison of Four Combination Chemotherapy Regimens Using Cisplatin in Treating Patients With Stage IVB, Recurrent, or Persistent Cancer of the Cervix

PRIMARY OBJECTIVES:

I. Compare the survival and response of patients with stage IVB, recurrent, or persistent
carcinoma of the cervix when treated with paclitaxel and cisplatin vs vinorelbine and
cisplatin vs gemcitabine and cisplatin vs topotecan and cisplatin.

II. Compare the toxic effects of these regimens in these patients. III. Compare the quality
of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment
arms.

ARM I: Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 1-4 hours
on day 2.

ARM II: Patients receive vinorelbine IV over 6-10 minutes on days 1 and 8 and cisplatin IV
over 1-4 hours on day 1.

ARM III: Patients receive gemcitabine IV over 30-60 minutes on days 1 and 8 and cisplatin as
in arm II.

ARM IV: Patients receive topotecan IV over 30 minutes on days 1-3 and cisplatin as in arm II.

In all arms, treatment repeats every 21 days for 6 courses in the absence of disease
progression or unacceptable toxicity.

Quality of life is assessed at baseline, before courses 2 and 5, and at 9 months after study
entry.

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

Inclusion Criteria:

- Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or
adenocarcinoma of the cervix

- Stage IVB, recurrent, or persistent disease

- Not amenable to curative surgery and/or radiotherapy

- At least 1 unidimensionally measurable lesion

- At least 20 mm by palpation, plain x-ray, CT scan, or MRI OR at least 10 mm by
spiral CT scan

- Biopsy confirmation required if lesion is less than 30 mm

- Target lesion must be outside of a previously irradiated field

- No craniospinal metastases

- Performance status - GOG 0-1

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Bilirubin no greater than 1.5 times normal

- Alkaline phosphatase no greater than 3 times normal

- AST no greater than 3 times normal

- Creatinine ≤ 1.2 mg/dL

- Creatinine > 1.2 mg/dL but < 1.5 mg/dL AND creatinine clearance ≥ 50 mL/min

- No bilateral hydronephrosis not alleviated by ureteral stents or percutaneous drainage

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No prior or concurrent malignancy within the past 5 years except nonmelanoma skin
cancer

- No prior malignancy whose treatment contraindicates the current study therapy

- No concurrent clinically significant infection

- No concurrent cytokines

- At least 6 weeks since prior chemoradiotherapy and recovered

- No prior chemotherapy (except when concurrently administered with radiotherapy)

- At least 3 weeks since prior radiotherapy and recovered

- Recovered from prior surgery