Current preventive treatment for recurrence after curative hepatectomy for liver metastases of colorectal carcinoma: A literature review of randomized control trials

Table 1 Randomized series of adjuvant intrahepatic arterial chemotherapy after surgical resection of hepatic metastases

Authors	Treatment protocol	Sample size(Tx/Ctl)	Observationtime	DFS Tx vs Ctl	OS Tx vs Ctl	Conclusions
Lygidakis et al[8]	Surgery+HAI chemoimmunotherapy	40 (20/20)	3 yr	NA	Median 20 vs	Beneficial
	vs surgery alone				11 (mo) (P < 0.05)
Asahara et al[9]	Surgery+HAI chemotherapy	38 (10/28)	NA	NA	3-yr 100% vs 60%	Beneficial
	vs surgery alone				4-yr 100% vs 47%,
					respectively (P < 0.05)
Rudroff et al[10]	Surgery+HAI 5-FU/MMC	30 (14/16)	5 yr	5-yr 15% vs	5-yr 25% vs 31%	Not
	vs surgery alone			23% (P>0.05)	(P > 0.05)	beneficial
Lorenz et al[11]	Surgery+HAI 5-FU/LV	226 (113/113)	NA	Median 14.2 vs	Median 34.5 vs	Not
	vs surgery alone			13.7 (mo) (P>0.05)	40.8 (mo) (P > 0.05)	beneficial
Kemeny et al[12]	Surgery+HAI FUDR/DEXA+IV	156 (74/82)	2 yr	2-yr 57% vs 42%	2-yr 86% vs 72%	Beneficial
	5-FU/LV vs surgery+IV 5-FU/LV			(P = 0.07)	(P = 0.03)
Tono et al[13]	Surgery+HAI 5-FU+oral 5-FU	19 (9/10)	62.2 (mo)	1-, 2-, 3-yr 77.8%,	1-, 2-, 3-yr 88.9%,	Beneficial
	vs surgery+oral 5-FU		(mean)	77.8%, 66.7% vs	77.8%, 77.8% vs
				50.0%, 30.0%, 20.0%	100.0%, 50.0%, and
				respectively (P = 0.045)	50.0% respectively
					(P = 0.2686)
Kemeny et al[14]	Surgery+HAI FUDR+IV 5-FU	109 (53/56)	NA	4-yr 46% vs 25%	Median 63.7 vs	Beneficial
	vs surgery			(P = 0.04)	49 (mo) (P = 0.60)

Tx: treatment; Ctl: control; DFS: disease-free survival; OS: overall survival; NA: not available.

Table 2 RCT studies on efficacy of systemic chemotherapy on prevention of recurrence

Authors	Treatment protocol	Sample size(Tx/Ctl)	Observationtime	DFS Tx vs Ctl	OS Tx vs Ctl	Conclusions
Lopez-Ladron et al[24]	Surgery+post-operative	38 (28/10)	Median 15	Median 15 vs 9	Median 30vs15	Not beneficial,
	chemotherapy vs surgery alone		(mo)	(mo) (P = 0.352)	(mo) (P = 0.066)	needing further study
Portier et al[23]	Surgery+post-operative	162 (81/81)	5 yr	5-yr 33% vs 24%	5-yr 51% vs 44%
	chemotherapy (FU/FA) vs surgery alone			(P > 0.05)	(P > 0.05)	Not beneficial

Tx: treatment; Ctl: control; DFS: disease-free survival; OS: overall survival; NA: not available.

Table 3 RCTs on efficacy of neoadjuvant chemotherapy

Authors	Treatment protocol	Sample size(Tx/Ctl)	Observationtime	DFS Tx vs Ctl		OS Tx vs Ctl	Conclusions
Lorenz et al[29]	Biweekly FOLFOX regimen × 6	40 (20/20)	NA	NA		NA	Induced significant remissions
	cycles vs biweekly FOLFOX regimen × 3 cycles						without increasing morbidity
Bathe et al[30]	5-FU+leukovorin+CPT-11						Ongoing

Tx: treatment; Ctl: control; DFS: disease-free survival; OS: overall survival; NA: not available.

Table 4 RCTs of immunotherapy

Authors	Treatment protocol	Sample size(Tx/Ctl)	Observationtime	DFS Tx vs Ctl	OS Tx vs Ctl	Conclusions
Lygidakis et al[8]	Surgery+post-operative HAI	40 (20/20)	3 yr	NA	Median	Beneficial
	immunochemotherapy				20 vs 11 (mo)
	vs surgery alone				(P < 0.05)
Lygidakis et al[33]	Post-operatively locoregional	45 (33/15)	NA	NA	Median	Beneficial
	immunochemotherapy vs				20.3 vs 9.9 (mo)
	post-operatively locoregional
	chemotherapy
Lygidakis et al[34]	Locoregional chemoimmunotherapy	122 (62/60)	NA	2-yr	2-yr 92% vs 75%	Beneficial
	with systemic chemotherapy vs			66% vs 48%	5-yr 73% vs 60%
	systemic immunochemotherapy
Elias et al[35]	Preoperative rIL-2 continuous	19 (12/7)	NA	NA	NA	Beneficial
	intravenous infusion					(well tolerated
						and reverse
						postoperative
						immunodepression)
Gardini et al[36]	Post-operative TIL+IL-2	45 (25/22)	NA	1-, 3-, and 5- yr	1-, 3-, and 5-yr	Not beneficial
	vs post-operative+chemotherapy			No difference	No difference

Tx: treatment; Ctl: control; DFS: disease-free survival; OS: overall survival; NA: not available.