Intensification Therapy for Locally Advanced Epidermoid Cancer of the Anal Canal - Phase III Intergroup Study

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.