Chemotherapy Plus Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer

OBJECTIVES:

• Compare the initial and total local and distant failure rates in patients with anal canal cancer treated with either fluorouracil (5-FU) plus mitomycin concurrently with radiotherapy or 5-FU plus cisplatin followed by 5-FU plus cisplatin concurrently with radiotherapy.
• Identify any differences in local control and colostomy rates at 2 years in patients treated with these regimens.
• Determine any difference in colostomy free, disease free, or overall survival in patients treated with these regimens.
• Compare the toxic effects of these regimens in these patients.
• Evaluate the prognostic effects of tumor markers P53 overexpression, human papilloma virus status, and enzyme HAP1 in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to gender, nodal status (positive vs negative), and primary tumor size (greater than 2 cm to 5 cm vs greater than 5 cm). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fluorouracil (5-FU) IV continuously over 96 hours beginning on days 1 and 29 and mitomycin IV on days 1 and 29 with concurrent radiotherapy.
• Arm II: Patients receive induction chemotherapy comprising 5-FU IV continuously over 96 hours beginning on days 1, 29, 57, and 85 and cisplatin IV over 1 hour on days 1, 29, 57, and 85. Beginning on day 57, patients receive concurrent radiotherapy.

In both arms, radiotherapy is administered daily, 5 days a week, for 5-6.5 weeks. Patients with T3, T4, or N+ lesions or T2 lesions with residual disease receive additional radiotherapy to a reduced field.

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

PROJECTED ACCRUAL: A total of 650 patients will be accrued for this study within 5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary squamous, basaloid, or cloacogenic carcinoma of the anal canal, other than carcinoma in situ

• T2-4, Any N, M0 (stage II or III)
• No local or regional recurrence after local excision or abdominal peritoneal resection

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm^3
• Absolute neutrophil count at least 1,800/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin less than 1.4 mg/dL

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 80 mL/min

Cardiovascular:

• No uncompensated heart disease
• No uncontrolled high blood pressure

Other:

• No AIDS
• No active systemic infection
• No uncontrolled diabetes
• No other prior malignancy within the past 5 years except nonmelanoma skin cancer
• No mental condition that would preclude study participation
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior epoetin alfa allowed in lieu of blood transfusions

Chemotherapy:

• At least 5 years since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 5 years since prior radiotherapy

Surgery:

• No prior surgery of anal canal except for biopsy of study site