Radiation Therapy With or Without Chemotherapy After Surgery in Treating Patients With Stage IB or Stage IIA Cervical Cancer
Radiation Therapy With or Without Chemotherapy After Surgery in Treating Patients With Stage IB or Stage IIA Cervical Cancer
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in
 chemotherapy use different ways to stop tumor cells from dividing so they stop growing or
 die. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet
 known whether giving radiation therapy with chemotherapy after surgery is more effective than
 radiation therapy alone after surgery in treating cervical cancer.

 PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or
 without chemotherapy after surgery in treating patients with stage IB or stage IIA cervical
 cancer.
OBJECTIVES: I. Compare relapse free and overall survival after radiation therapy with or
 without the sequential use of chemotherapy in patients with node positive stage IB or IIA
 cervical cancer. II. Compare the toxic effects of these two treatments in this patient
 population. III. Study the effect of the addition of chemotherapy on the pattern of relapse
 in these patients.

 OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
 institution, stage, site of lymph node involvement, parametrial invasion, resection margin
 status, diameter of the primary lesion, and preoperative brachtherapy. Patients are assigned
 to one of two treatment arms and begin therapy within 6 weeks of surgery. Arm I: Patients
 receive radiation therapy to the pelvis with or without brachytherapy and/or para-aortic
 irradiation for 4-5 weeks. Arm II: Patients receive radiation therapy as in arm I plus 1 of 5
 different cisplatin-based combination chemotherapy regimens. The patients preferably receive
 chemotherapy before radiation therapy, unless doubtful or positive margins are present, then
 radiation therapy is given first. Regimen I: Cisplatin and fluorouracil are administered on
 days 1 and 2 of a 21 day cycle. Patients receive 4 cycles of therapy. Regimen II: Bleomycin
 is administered on day 1 and cisplatin and ifosfamide are administered on day 2 of a 21 day
 cycle. Patients receive 4 cycles of therapy. The regimen may also be given without bleomycin.
 Regimen III: Patients receive vindesine on days 1 and 8, cisplatin on day 1, bleomycin on
 days 2-4, and mitomycin on day 5 (cycles 1 and 3 only). Each cycle lasts 21 days and patients
 receive 4 cycles of therapy. Regimen IV: Cisplatin and vinblastine are administered on day 1
 and bleomycin is administered on days 1, 8, and 15 of a 21 day cycle. Each patient receives 4
 cycles of therapy. Regimen V: Patients receive cisplatin and methotrexate on day 1 of each 14
 day cycle. Patients receive 6 cycles of therapy. Patients are followed every 3 months for the
 first 2 years, every 6 months for the next 3 years, then annually for the next 5 years.

 PROJECTED ACCRUAL: Approximately 700 patients will be accrued for this study within 4 years.
DISEASE CHARACTERISTICS: Histologically proven stage IB or IIA cervical cancer Squamous
 cell carcinoma Adenosquamous cell carcinoma Adenocarcinoma Pelvic and/or common iliac or
 para-aortic lymph node involvement Undergone a radical hysterectomy, complete pelvic
 lymphadenectomy, and resection of any enlarged common iliac or para-aortic lymph nodes No
 clear cell carcinoma or small cell carcinoma with neuroendocrine differentiation Resectable
 disease

 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not
 specified Hematopoietic: WBC at least 3500/mm3 Platelet count at least 100,000/mm3 Hepatic:
 Bilirubin no greater than 14.6 mg/dL Renal: Creatinine no greater than 1.356 mg/dL
 Creatinine clearance at least 60 mL/min Pulmonary: Maximum breathing capacity at least 30
 L/min FEV1 at least 1.0 L No signs of respiratory insufficiency Other: No potentially
 active site of infection (e.g., fistula or abscesses) No prior or concurrent second
 malignancy except adequately treated basal cell carcinoma of the skin

 PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified
 Endocrine therapy: Not specified Radiotherapy: No preoperative external radiotherapy
 Surgery: See Disease Characteristics