Radiation Therapy Plus Paclitaxel and Cisplatin in Treating Patients With Cervical Cancer

OBJECTIVES:

• Determine the toxicity of radiotherapy plus paclitaxel and cisplatin used as radiosensitization in patients with stage IB2, IIA, IIB, IIIB, or IVA invasive carcinoma of the cervix.
• Determine the maximum tolerated dose of paclitaxel when combined with cisplatin plus radiotherapy in these patients.
• Determine the effects of this regimen at the maximum tolerated dose on progression-free survival and overall survival in these patients.
• Determine the site of local or distant recurrence in these patients after treatment with this regimen.

OUTLINE: This is a dose escalation study of paclitaxel.

Patients undergo external beam radiotherapy (RT) to the pelvic region 5 days a week during weeks 1-5. Patients receive paclitaxel IV over 1 hour immediately followed by cisplatin concurrently with pelvic field radiotherapy on days 1, 8, 15, 22, 29, and 36. Patients undergo low-dose rate (LDR) OR high-dose rate (HDR) brachytherapy. For patients undergoing LDR brachytherapy, intracavitary implants are inserted 1 or 2 times within 3 weeks after completion of external beam RT. For patients undergoing HDR brachytherapy, intracavitary implants are inserted once a week for 5 weeks beginning during week 4 of external beam RT. Patients may receive a parametrial boost.

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 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the MTD as above.

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

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 3-7 years.

DISEASE CHARACTERISTICS:

• Histologically proven stage IB2, IIA, IIB, IIIB, or IVA invasive carcinoma of the uterine cervix

• Any cell type
• No metastases to para-aortic lymph nodes, scalene nodes, or to other organs outside the radiation field at time of original staging
• Study entry required within 8 weeks of diagnosis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• GOG 0-2

Life expectancy:

• More than 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) that would require modification of radiation fields

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy for this or any prior malignancy

Endocrine therapy:

• No prior endocrine therapy

Radiotherapy:

• No prior pelvic or abdominal radiotherapy for this malignancy
• No prior radiotherapy for any other prior malignancy
• No more than 1 month interval between surgery and radiotherapy

Surgery:

• See Radiotherapy

Other:

• No other prior therapy for this malignancy
• Stent or nephrostomy tube required if ureteral obstruction present