Anal cancer treatment: Current status and future perspectives

Table 2 Studies evaluating recent treatment options in locally advanced anal cancer

	Study	Patients, n	Protocol	RR	OS	DFS	CFS
Induction chemotherapy in LAAC	Nilsson et al[36], 2005Population-based series	308 invasive SCAC	- Arm A: Neoadjuvant platinum CT followed by RT alone	CR: 92%	63%	NA	NA
		142 locally advanced	-Arm B: RT with or without Bleomycin	CR: 76% P < 0.01	44% P < 0.05
	Meropol et al[37], 20081 Phase II	45	Induction: 2 28-d cycles (FU + cisplatin) followed by 2 28-d cycles (FU + mitomycin) with concurrent split-course radiation	CR: 82%	68% at 4 yr	61% at 4 yr	50%
	Peiffert et al[38], 20122 Phase III RCT	283	-Arm A: 2 ICT cycles (5-FU + cisplatin) then RCT and standard dose boost (SD: 15 Gy)	NA	NA	NA	69.6%
			-Arm B: 2 ICT, RCT and high dose boost (HD: 20-25 Gy)				82.4%
			-Arm C: RCT and SD boost				77.1%
			-Arm D: RCT and HD boost				72.7%
Combination of MMC and cisplatin in LAAC	Crehange et al[39], 2007 Phase II	21	1st sequence:RT 36 Gy over 4 wk	CR: 90.5%	NA	NA	NA
			2nd sequence: 23.4 Gy over 2.5 wk, gap 16 d
			MMC and CDDP
	Matzinger et al[40], 20093 Phase II	80	RT: 36Gy + 2 wk gap + 23.4 Gy
			-Arm A: MMC + Cisplatin + RT	RR: 91.9%	NA	NA	NA
			-Arm B: MMC + 5-FU + RT	RR: 79.5%
Targeted therapy in LAAC	Olivatto et al[48], 2013 Phase I	21	Cetuximab + RT + 5-FU + cisplatin	pCR: 95%	NA	NA	NA
	Deutsch et al[49], 2013 Phase II	16	Cetuximab + RT + 5-FU + cisplatin	CR: 55%PR: 45%	92% at 1 yr	NA	67% at 1 yr
Cisplatin in LAAC	Eng et al[50], 20134 Retrospective single institution analysis	197 (41% stage II, 46% stage III, 24% N2-N3)	Weekly (20 mg/m2) or daily (4 mg/m2) cisplatin with 5-FU and RT	CR: 94%	86% at 5 yr	81% at 5 yr	88% at 5 yr

¹After induction, 8 CR and 21 PR. A third cycle of FU and cisplatin with radiation boost was given to patients with persistent primary site disease or bulky N2 or N3 disease at presentation;

²Considering the 2 × 2 factorial analysis, the 5-year CFS was 76.5% vs 75% in groups A and B vs C and D, respectively (ICT effect; P = 0.37), and 73.7% vs 77.8% in groups A and C vs B and D, respectively (RT-dose effect; P = 0.067);

³In the first arm, 9 patients discontinued treatment, with 9 grade 3 hematologic effects. In the second arm, 2 discontinued treatment, and no grade 3 hematologic effects were reported;

⁴The local recurrence rate was 11% after the median follow-up of 8.6 yr, and 8% of the patients developed distal metastases. LAAC: Locally advanced anal cancer; MMC: Mitomycin C; RR: Response rate; NA: Not availiable; RT: Radiation therapy; 5-FU: 5-Fluorouracil; CR: Complete response; CFS: Colostomy-free survival; OS: Overall survival; DFS: Disease free survival; RT: Radiation therapy.