Chemotherapy and Radiation Therapy With or Without Surgery in Treating Patients With Stage I Cancer of the Cervix
Chemotherapy and Radiation Therapy With or Without Surgery in Treating Patients With Stage I Cancer of the Cervix
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. It is not yet known which regimen of radiation therapy combined with chemotherapy, with
 or without surgery, is more effective in treating early cancer of the cervix.

 PURPOSE: Randomized phase III trial to compare the effectiveness of surgery followed by
 different regimens of radiation therapy and chemotherapy with that of chemotherapy and
 radiation therapy alone in treating patients who have stage I cancer of the cervix.
OBJECTIVES:

 -  Compare progression-free survival and survival of patients with stage IB2 carcinoma of
 the cervix after radical hysterectomy with tailored chemoradiotherapy vs primary
 chemoradiotherapy.

 -  Compare the toxicity of these regimens in these patients.

 -  Compare the health-related quality of life of patients treated with these regimens.

 OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment
 arms.

 -  Arm I: (Surgery followed by chemoradiotherapy): Patients undergo exploratory laparotomy
 followed by radical hysterectomy and bilateral pelvic and para-aortic lymphadenectomy.
 Depending on the findings at surgery, the radical hysterectomy and lymphadenectomy are
 either completed or aborted.

 -  Aborted hysterectomy: Patients with aborted hysterectomy are assigned to 1 of 3
 groups, depending on the findings at surgery.

 -  Group 1: Within 4 weeks of surgery, patients undergo pelvic radiotherapy 5
 times weekly for 4-6 weeks and intracavitary irradiation during or after
 external radiotherapy. Patients also receive concurrent cisplatin IV over 1
 hour once weekly for a total of 5-6 doses.

 -  Group 2: Patients receive radiotherapy and cisplatin as in group 1 with
 additional extended field radiotherapy.

 -  Group 3: Patients receive further treatment at the discretion of the
 investigator.

 -  Completed hysterectomy: Patients completing the radical hysterectomy are assigned
 to 1 of 3 groups, depending on the findings at surgery.

 -  Group A: Patients receive treatment as in group 1 above without intracavity
 irradiation.

 -  Group B: Patients receive treatment as in group 2 above without intracavity
 irradiation.

 -  Group C: Patients receive no further treatment.

 -  Arm II (Primary chemoradiotherapy): Patients undergo pelvic radiotherapy 5 times weekly
 for 4-6 weeks and intracavity irradiation during or after external radiotherapy.
 Patients also receive concurrent cisplatin IV over 1 hour once weekly for a total of 6
 doses.

 Quality of life is assessed at baseline, during week 5 of therapy, and then at 3, 6, and 12
 months.

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

 PROJECTED ACCRUAL: A total of 740 patients (370 per treatment arm) will be accrued for this
 study within 7.5 years.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed stage IB2 invasive carcinoma of the uterine cervix of one of
 the following types:

 -  Squamous cell carcinoma

 -  Adenocarcinoma

 -  Adenosquamous carcinoma

 -  Primary, previously untreated disease

 -  Exophytic cervical lesions greater than 4 cm in diameter OR

 -  Cervical expansion to greater than 4 cm in diameter, presumed to be the result of
 principal involvement with cancer

 -  No evidence of extrauterine disease other than pelvic lymph node involvement (by
 clinical and radiographic examinations)

 -  No para-aortic lymph nodal disease (suspected on CT scan, MRI, positron-emission
 tomography, or lymphangiogram) unless nodes are confirmed to be pathologically
 negative (by CT-guided biopsy or extraperitoneal lymph node dissection)

 -  Eligible for radical hysterectomy and lymph node dissection

 PATIENT CHARACTERISTICS:

 Age

 -  18 and over

 Performance status

 -  GOG 0-2

 Life expectancy

 -  Not specified

 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

 -  Alkaline phosphatase no greater than 3 times normal

 Renal

 -  Creatinine no greater than 2.0 mg/dL

 -  No renal abnormalities requiring modification of radiation fields

 Gastrointestinal

 -  No gastrointestinal bleeding

 -  No intestinal obstruction

 Other

 -  Not pregnant

 -  Negative pregnancy test

 -  No septicemia or severe infection

 -  No other invasive malignancy with any evidence of disease within the past 5 years
 except nonmelanoma skin cancer

 -  No circumstances that would preclude study completion or required follow-up

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  Not specified

 Chemotherapy

 -  No prior chemotherapy

 Endocrine therapy

 -  Not specified

 Radiotherapy

 -  No prior radiotherapy

 Surgery

 -  See Disease Characteristics

 -  No prior hysterectomy (total or subtotal)