OBJECTIVES:

• Compare the efficacy of concurrent chemotherapy and radiotherapy with or without neoadjuvant chemotherapy with fluorouracil and cisplatin in patients with stage II or III anal canal cancer.
• Compare the efficacy of two levels of radiation dose in patients with stage II or III anal canal cancer.
• Compare the sphincter conservation of the anus by these regimens.
• Compare the effect of these regimens on survival and quality of life of these patients.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized to one of four treatment arms.

• Arm I: Patients receive induction chemotherapy consisting of fluorouracil IV over 24 hours on days 1-4 and cisplatin IV over 1 hour on day 1 or 2 every 4 weeks for 2 courses. Beginning 4 weeks later, patients receive chemoradiotherapy. This regimen consists of fluorouracil IV over 24 hours on days 1-4 and cisplatin IV over 1 hour on day 1 or 2 and repeated 4 weeks later, plus pelvic radiotherapy beginning on day 1 and continuing for 5 weeks (once a day, 5 days/week). Patients receive low dose radiotherapy directly to the tumor beginning 3 weeks later and continuing for 2 weeks.
• Arm II: Patients receive induction chemotherapy and chemoradiotherapy as in arm I, plus high dose radiotherapy directly to the tumor.
• Arm III (control arm): Patients receive chemoradiotherapy and low dose radiotherapy to the tumor as in arm I.
• Arm IV: Patients receive chemoradiotherapy and high dose radiotherapy to the tumor as in arm II.

After study treatment is completed, patients with nonfixed inguinal tumors may undergo surgical resection followed by radiotherapy or radiotherapy alone. Patients with fixed inguinal tumors may receive further radiotherapy alone.

Quality of life is assessed before treatment, at 2 months after completion of treatment, and at 5 years.

Patients are followed every 4 months for 2 years, every 6 months for 3 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 350 patients will be accrued for this study within 4 years.