Trial Information

A Phase III Randomized Study of 5-Fluorouracil, Mitomycin-C, and Radiotherapy Versus 5-Fluorouracil, Cisplatin, and Radiotherapy in Carcinoma of the Anal Canal

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.