Radiation Therapy and Cisplatin With or Without Amifostine for Patients With Stage IIIB or IVA Cervical Cancer

OBJECTIVES:

• Determine the feasibility and tolerability of external beam radiotherapy, brachytherapy, and cisplatin in patients with para-aortic or high common iliac lymph node-positive carcinoma of the uterine cervix.
• Determine the feasibility and tolerability of this regimen with the addition of amifostine in these patients.
• Determine the efficacy of these 2 regimens, in terms of improving pelvic and para-aortic tumor control and distant metastases, in these patients.

OUTLINE:

• Phase I: Patients undergo external beam radiotherapy to the pelvis and para-aortic region 5 days a week for 5 weeks. Patients also undergo either intracavitary low-dose rate (LDR) brachytherapy in 2 applications beginning within 2 weeks after completion of external beam radiotherapy at 2-3 week intervals or 6 fractions of high-dose rate intracavitary brachytherapy over 8 weeks beginning as early as week 2 of external beam radiotherapy. Patients also receive cisplatin IV over 1 hour weekly for 6 weeks concurrently with external beam radiotherapy and once with LDR brachytherapy. Phase II proceeds only if toxicity in phase I is within expected parameters.
• Phase II: Patients receive external beam radiotherapy, brachytherapy, and cisplatin as in phase I. Patients also receive amifostine subcutaneously daily just before external beam radiotherapy and cisplatin. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

DISEASE CHARACTERISTICS:

• Histologically proven, locally advanced carcinoma of the uterine cervix

• TNM classification stage IIIB or IVA
• Disease metastatic to para-aortic or high common iliac lymph nodes

• Prior complete surgical resection of involved lymph nodes or gross residual tumor involvement of a lymph node allowed
• The following cellular types are eligible:

• Squamous cell carcinoma
• Adenocarcinoma
• Adenosquamous carcinoma
• The following cellular types are ineligible:

• Small cell carcinoma
• Carcinoid tumor
• Glassy cell carcinoma
• Clear cell carcinoma
• Cystadenocarcinoma
• No metastatic disease outside of the pelvis (except to the para-aortic nodes)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• At least 6 months

Hematopoietic

• White blood cell count (WBC) at least 3,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• Alanine amino transferase (ALT) no greater than 2 times normal

Renal

• Creatinine no greater than 1.5 mg/dL (urinary diversion allowed)
• Corrected calcium normal

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent significant medical condition that would preclude study participation
• No insulin-dependent diabetes
• No other malignancy within the past 3 years except cutaneous basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior pelvic irradiation except transvaginal radiotherapy to control bleeding

Surgery

• See Disease Characteristics
• No prior tumor-directed surgery except lymph node biopsy/staging