• 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 ]
  

• 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 ]
  

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.

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