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.

Condition	Treatment or Intervention	Phase
cervical squamous cell carcinoma cervical adenocarcinoma stage IB cervical cancer stage IIA cervical cancer cervical adenosquamous cell carcinoma	Drug: bleomycin  Drug: cisplatin  Drug: fluorouracil  Drug: ifosfamide  Drug: methotrexate  Drug: mitomycin  Drug: vinblastine  Drug: vindesine	Phase III

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--Prior/Concurrent Therapy--

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

--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

United Kingdom, England
      Derbyshire Royal Infirmary, Derby,  England,  DE1 2QY,  United Kingdom
United Kingdom, Scotland
      Beatson Oncology Centre, Glasgow,  Scotland,  G11 6NT,  United Kingdom

Study chairs or principal investigators

Sergio L. Pecorelli,  Study Chair,  EORTC Gynecological Cancer Cooperative Group   
R. Paul Symonds,  Study Chair

Study ID Numbers:  CDR0000066064; EORTC-55954; COSA; EU-98061; NSGO-CC-9502
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003209
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08