• Complete response rate at 6 months [ Designated as safety issue: No ]
• Acute toxicity as measured up to 4 weeks after chemoradiation [ Designated as safety issue: Yes ]
• Recurrence-free survival [ Designated as safety issue: No ]

• Complete response rate at 6 months
• Acute toxicity as measured up to 4 weeks after chemoradiation
• Recurrence-free survival

• Colostomy rate [ Designated as safety issue: No ]
• In field recurrence rate as measured by confirmed disease within radiation therapy field [ Designated as safety issue: No ]
• Cause-specific and overall survival [ Designated as safety issue: No ]

• Colostomy rate
• In field recurrence rate as measured by confirmed disease within radiation therapy field
• Cause-specific and overall survival

RATIONALE: Radiation therapy uses high-energy x-rays to kill 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 if fluorouracil plus radiation therapy is more effective with or without additional chemotherapy in treating anal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil plus radiation therapy with or without additional chemotherapy in treating patients who have primary anal cancer.

OBJECTIVES:

• Compare the response rates in patients with primary epidermoid anal cancer treated with radiotherapy and fluorouracil with either mitomycin or cisplatin and with or without maintenance therapy.
• Compare local control and prevention or delay of disease dissemination in patients treated with these regimens.

OUTLINE: This is randomized, open-label, multicenter study. Patients are randomized to one of four treatment arms.

All patients undergo radiotherapy daily 5 days a week for 5.5 weeks. All patients also receive fluorouracil IV continuously over days 1-4 and 29-32.

• Arm I: Patients receive mitomycin IV on day 1.
• Arm II: Patients receive cisplatin IV on days 1 and 29.
• Arm III: Patients receive mitomycin as in arm I and maintenance therapy comprising fluorouracil IV continuously over days 1-4 and cisplatin IV on day 1 beginning 4-8 weeks after completion of primary therapy and repeating once 3 weeks later.
• Arm IV: Patients receive cisplatin as in arm II and maintenance therapy as in arm III.

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

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 600 patients (150 per treatment arm) will be accrued for this study.

• Drug: cisplatin
• Drug: fluorouracil
• Drug: mitomycin C
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed primary epidermoid anal cancer

  • Squamous cell
  • Basaloid
  • Cloacogenic
• No adenocarcinoma, malignant melanoma, mucoepidermoid carcinoma, lymphoma, or microinvasive anal intraepithelial neoplasia (without evidence of invasive disease) in the anal canal or margin
• No metastatic disease

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 10 g/dL

Hepatic:

• Liver function tests no greater than 2 times normal

Renal:

• Glomerular filtration rate at least 50 mL/min

Cardiovascular:

• No cardiovascular disease
• No uncontrolled angina pectoris
• No heart failure
• No clinically significant cardiac arrhythmias

Other:

• HIV negative
• No other significant concurrent illness
• Not predominately bed-bound or frail
• No severe sepsis
• No other prior or concurrent cancer or illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to pelvis

Surgery:

• Not specified

Other:

• No prior therapy for anal cancer