RATIONALE: Drugs used in chemotherapy, such as mitomycin, fluorouracil, and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known whether radiation therapy and mitomycin are more effective when combined with fluorouracil or with cisplatin in treating anal cancer .

PURPOSE: Randomized phase II/III trial to compare the effectiveness of radiation therapy and mitomycin combined with either fluorouracil or cisplatin in treating patients who have locally advanced anal cancer.

Condition	Treatment or Intervention	Phase
squamous cell carcinoma of the anus stage II anal cancer stage IIIA anal cancer stage IIIB anal cancer	Drug: cisplatin  Drug: fluorouracil  Drug: mitomycin  Procedure: chemotherapy  Procedure: radiation therapy	Phase II Phase III

OBJECTIVES: Phase II

• Compare the early clinical response (tumor response at 8 weeks) of patients with locally advanced anal cancer treated with radiotherapy with mitomycin and cisplatin vs mitomycin and fluorouracil.
• Compare the feasibility of these regimens in these patients.
• Compare the acute toxicity of these regimens in these patients.
• Compare patient compliance to these regimens.

Phase III

• Compare the event-free survival of patients treated with these regimens.
• Compare colostomy-free, disease-free, and overall survival of patients treated with these regimens.
• Compare locoregional control in patients treated with these regimens.
• Compare the late toxicity of these regimens in these patients.
• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, T stage (T2 vs T3 vs T4), and nodal status (N0 vs N+). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy once daily 5 days a week on weeks 1-4, 7-8, and 3 days of week 9 (total of 33 fractions). Patients concurrently receive fluorouracil IV continuously on days 1-26 and 43-59 and mitomycin IV over 15 minutes on days 1 and 43.
• Arm II: Patients receive radiotherapy and mitomycin as in arm I and cisplatin IV over 1 hour on days 1, 8, 15, 22, 43, 50, and 57. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, at weeks 12 and 26, and then every 6 months for 2 years.

Patients are followed every 2 weeks for 8 weeks, at week 26, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 678 patients (80 [40 per treatment arm] for phase II and 598 [299 per treatment arm] for phase III) will be accrued for this study within 2-5 years.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell anal carcinoma
• Keratinizing or non-keratinizing
• The following stages are eligible:
• T2, N0, M0 with maximum tumor diameter at least 4 cm
• T3-T4, N0, M0
• Any T, N1-N3, M0
• Tumor located in the anal canal OR in the anal margin and infiltrating the anal canal
• No primary adenocarcinoma of the anus
• Measurable disease

PATIENT CHARACTERISTICS: Age

• 18 to 75

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count greater than 2,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic

• Not specified

Renal

• Creatinine less than 1.4 mg/dL

Cardiovascular

• No grade I angina pectoris with clinical symptoms within the past 3 months
• No grade II-IV angina pectoris within the past 3 months
• No stage II or greater distal arteritis

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other prior malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No other concurrent radiotherapy

Surgery

• No prior colostomy

Other

• No prior treatment for anal cancer

France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France; Recruiting
Germany
      Evangelisches Bethesda Krankenhaus GmbH, ESSEN,  D-45355,  Germany; Recruiting

Study chairs or principal investigators

Jean Francois Bosset, MD,  Study Chair,  CHR de Besancon - Hopital Jean Minjoz   
Felicitas Roelofsen, MD,  Study Chair,  Evangelisches Bethesda Krankenhaus GmbH   

Study ID Numbers:  CDR0000327845; EORTC-22011; EORTC-40014
Record last reviewed:  August 2003
Record first received:  September 10, 2003
ClinicalTrials.gov Identifier:  NCT00068744
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-17