Chemotherapy Followed By Surgery Vs Radiotherapy Plus Chemotherapy in Patients With Stage IB or II Cervical Cancer
Chemotherapy Followed By Surgery Vs Radiotherapy Plus Chemotherapy in Patients With Stage IB or II Cervical Cancer
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Giving chemotherapy drugs before surgery may shrink the tumor so
 that it can be removed during surgery. Radiation therapy uses high-energy x-rays to kill
 tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. It is
 not yet known whether chemotherapy is more effective followed by surgery or combined with
 radiation therapy in treating cervical cancer.

 PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by
 radical hysterectomy with that of chemotherapy plus radiation therapy in treating patients
 who have stage IB or stage II cervical cancer.
OBJECTIVES:

 -  Compare the overall and progression-free survival of patients with stage IB2, IIA, or
 IIB cervical cancer treated with neoadjuvant cisplatin-based chemotherapy followed by
 radical hysterectomy vs standard therapy comprising concurrent radiotherapy and
 cisplatin-based chemotherapy.

 -  Compare the toxicity of these regimens in these patients.

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

 OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
 participating center, FIGO stage, age (18 to 50 vs 51 to 75), and histological subtype
 (adenomatous vs non-adenomatous component). Patients are randomized to 1 of 2 treatment arms.

 -  Arm I: Patients receive neoadjuvant cisplatin-based chemotherapy on day 1. Treatment
 repeats every 21 days. Within 6 weeks after the last chemotherapy course, patients
 undergo a type III-V Piver-Rutledge radical hysterectomy. Patients with positive lymph
 nodes or tumor invasion into the parametria or less than 5 mm from the resection borders
 after surgery receive standard adjuvant external beam radiotherapy once daily, 5 days a
 week, for 5-5.6 weeks (25-28 treatment days) followed by external boost radiotherapy or
 brachytherapy for 1 or 2 days.

 -  Arm II: Patients receive standard therapy comprising radiotherapy as in arm I
 concurrently with cisplatin-based chemotherapy once weekly for 6 weeks. Adjuvant
 hysterectomy is allowed, but not recommended, in case of histologically proven residual
 tumor.

 Treatment in both arms continues in the absence of disease progression or unacceptable
 toxicity. For patients in both arms, cisplatin may be combined with other chemotherapeutics
 as long as the minimum platinum dose is given.

 Quality of life is assessed at baseline and at 6, 12, 18, and 24 months.

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

 PROJECTED ACCRUAL: A total of 686 patients (343 per treatment arm) will be accrued for this
 study within 3.8 years.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed cervical cancer, including the following subtypes:

 -  Squamous cell carcinoma

 -  Adenosquamous cell carcinoma

 -  Adenocarcinoma (excluding small cell, clear cell, and other rare variants of the
 classical adenocarcinoma)

 -  FIGO stage IB2, IIA (greater than 4 cm), or IIB

 PATIENT CHARACTERISTICS:

 Age:

 -  18 to 75

 Performance status:

 -  WHO 0-2

 Life expectancy:

 -  Not specified

 Hematopoietic:

 -  Absolute neutrophil count greater than 1,500/mm^3

 -  Platelet count greater than 100,000/mm^3

 Hepatic:

 -  Bilirubin less than 1.46 mg/dL

 Renal:

 -  Creatinine clearance greater than 60 mL/min

 Other:

 -  No other prior or concurrent malignancy except adequately treated basal cell skin
 cancer

 -  No psychological, familial, sociological, or geographical condition that would
 preclude study

 -  Not pregnant

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  Not specified

 Chemotherapy:

 -  No prior chemotherapy

 Endocrine therapy:

 -  Not specified

 Radiotherapy:

 -  No prior radiotherapy

 Surgery:

 -  Not specified

 Other:

 -  No other concurrent anticancer agent