Table 3.

Key phase 3 trials evaluated radiation versus chemoradiation therapy, induction or maintenance chemotherapy, or high or standard dose booster radiation therapy in patients with stage 1–3 and all canal cancer.

Trial	N	Arms	Accrual Period	Follow Up Months	Response	Local Failure	Survival
UKCCR [49]	585	RT vs. CRT	1987–1991	42	Good clinical response at 6 wks: 91% vs. 92% (CR 30% to 39%)	59% vs. 36% (P < 0.0001)	3-year anal cancer mortality (39% vs 28%) p = 0.02 3-year OS 58% vs 65% p = 0.25
EORTC [50]	110	RT vs. CRT	1987–1994	60	CR 54% vs. 80%	18% difference in loco-regional failure (0.002)	5-year survival 56% for whole group
RTOG 87-04/EORTC 1289 [51]	310	MMC plus 5FU or 5FU alone	1998–1991	48	Post-treatment positive biopsies 15% vs. 7.7% (p = 0.13)	Colostomy rates (9% vs. 22%; P = 0.002)	DFS favoring MMC 73% vs. 51%; P = 0.0003
RTOG 98–11 [52]	682	5FU-MMC vs. induction 5FU-CDDP for 2 cycles followed by concurrent 5FU-CDDP	1998–2005	60	NR	20% vs. 26.4% (p = 0.08)	5-yr CFS, 71.9% vs. 65.0% (p = 0.05) 5-year DFS, (67.8% vs. 57.8%; P = 0.006) 5-year OS, 78.3% vs. 70.7%; P = 0.026).
ACTII [53]	940	2 × 2 MMC vs. 5FU-CDDP Maintenance 5FU-CDDP for 2 cycles vs. no-maintenance	2001–2008	61	90.5% with MCC vs. 89.6% with cisplatin	Colostomy rates 11–16 (p = NS)	3-year PFS 70% vs. 69% p = 0·70 with maintenance 3-year PFS 69% vs. 69% p = 0·NS with CPDD vs. MMC
ACCORD [54]	307	2 × 2 Induction chemo vs. no induction High dose boost vs. standard doses boost	199–2005	50	CR or major response with sphincter preservation 92% ICT/SD, 97% ICT/HD, 86% CRT/SD, 94% for CRT /HD		5-year DFS70% ICT/SD; 78% ICT/HD; 67% CRT/SD; 68% CRT /HD 5-year OS 74.5% ICT 71% no ICT

CRT = chemoradiation therapy; CDDP = cisplatin; CFS: Colostomy free survival; DFS = disease-free survival; Good clinical response = complete or >50% reduction in tumor; HD = high dose; ICT = induction chemotherapy; MMC= mitomycin; NR = not reported; NS= not reported; OS = overall survival; RT = radiation therapy; SD = Standard dose.