Paclitaxel, Topotecan, and Cisplatin in Treating Patients With Advanced, Persistent, or Recurrent Cervical Cancer

OBJECTIVES:

Primary

• Estimate the antitumor activity of the combination of paclitaxel, topotecan, and cisplatin in patients with advanced, persistent, or recurrent carcinoma of the cervix.
• Determine the nature and degree of toxicity for this drug regimen in these patients.

Secondary

• Determine the duration of progression-free survival and overall survival.
• Determine the impact of prior chemoradiation on response to treatment.

OUTLINE: This is an open-label study.

Patients receive paclitaxel IV over 1 hour followed by topotecan IV over 30 minutes and cisplatin IV over 1 hour on days 1 and 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 66 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Advanced, persistent, or recurrent squamous or nonsquamous cell carcinoma of the cervix with documented disease progression

• Histologic confirmation of the original primary tumor is required
• Disease must be measurable in at least one dimension by conventional techniques, including palpation, plain x-ray, CT scan, or MRI

• Measurable disease is defined as at least one lesion that can be accurately measured
• Each lesion must be ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
• Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days after completion of radiation therapy

PATIENT CHARACTERISTICS:

• GOG performance status 0-2
• Platelet count ≥ 100,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• SGOT and alkaline phosphatase ≤ 2.5 times ULN
• Neuropathy (sensory and motor) ≤ grade 1
• No active infection requiring antibiotics
• No evidence of more than one malignancy present within the past 5 years

• Nonmelanoma skin cancer allowed
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior therapy with cytotoxic drugs for advanced or recurrent cervical carcinoma

• Prior cisplatin as a radiosensitizer for primary treatment of disease allowed
• No previous cancer treatment that contraindicates study treatment
• No prior radiotherapy to any portion of the abdominal cavity or pelvis except for the treatment of cervical cancer
• No prior chemotherapy for any abdominal or pelvic tumor except for the treatment of cervical cancer
• Recovered from effects of recent surgery, radiotherapy, or other therapy
• At least 4 weeks since prior radiotherapy
• More than 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin and free of recurrent or metastatic disease
• More than 3 years since prior adjuvant chemotherapy for localized breast cancer provided patient is free of recurrent or metastatic disease
• No hormonal therapy directed at the malignant tumor within the past week
• Concurrent hormone replacement therapy is permitted
• No concurrent amifostine or other protective reagents