Table 2.

Dosage and toxicities of trials evaluating triplet chemotherapy alone, in combination with bevacizumab or with anti-EGFRs

Author	phase	regimen	N	irinotecan		Oxaliplatin		5-FU		Median cycle	Gr3-4 toxicity (%)	Gr3-4 neutropenia (FN) (%)	Gr3-4 diarrhea (%)
				Dose (mg/m2)	rDI	Dose (mg/m2)	rDI	Dose mg/m2)	rDI
Triplet regimen
Falcone A, et al. 2007	III	FOLFOXIRI	122	165	82	85	83	3200	82	11		50 (5)	20
Masi G, et al. 2004	II	FOLFOXIRI	32	165	86	85	89	3200	90	12		59 (12)	16
Souglakos J, et al. 2006	III	FOLFOXIRI	137	150	85	65	84	Bolus 800 CI 1200	88	10		35 (9)	27.7
Souglakos J, et al. 2002	II	FOLFOXIRI	31	150	85	65	84	Bolus 800 CI 1200	88	12		45 (6)	32
Ychou, et al. 20	II	FOLFIRINOX	34 Liver limited	180	87	85	88	Bolus 400 CI 2400	91	9.5	76.5	64.8 (3)	29.4
Sunakawa Y, et al. 2012	I	FOLFOXIRI	6 3	150 165	79 88	85 85	79 88	2400 2400	79 88	8.5		27 (0)	0
Combination with bevacizumab
Loupakis F, et al. 2014	III	FOLFOXIRI+bev	252	165	74	85	75	3200	73	11		50.0 (8.8***)	18.8
Masi G, et al. 2010	II	FOLFOXIRI+bev	57	165	85	85	85	3200	84	12		49 (2)	14
Gruenberger T, et al. 2015	II	FOLFOXIRI+bev	41 Liver limited	165		85		3200		6	95	50 (13)	30
Satake, et al. 2015	I	FOLFOXIRI+bev	6	165	87	85	87	3200	90			67 (0)	0
Combination with anti-EGFR antivbody
Saridaki Z, et al. 2012	II	FOLFOXIRI+cet	30 KRAS wt	150	85.3	65	93.2	Bolus 800 CI 1200	83.2			23.3 (6.7)	53.3
Assenat E, et al. 2011	II	FOLFIRINOX+cet	42	180	86	85	85	Bolus 400 CI 2400	92	9	88.1	38.0 (4.8)	52.4
Folprecht G, et al. 2014	I	FOLFOXIRI+cet	6	125		85		3200		9.7		28.6	28.6
Fornaro L, et al. 2013	II	FOLFOXIRI+pani	37 RAS/BRAF wt	150	74	85	75	2400	76	11		48 (5)	35

^*TTP

^**patients underwent R0/R1 resection or all patients resected

^***Gr3-4

Abbreviation: NA, not applicable; NR, not reached; FIr-bev/FOx, 5-FU plus alternating irinotecan/bev or oxaliplatin; FN, febrile neutropenia; rDI, relative dose intensity; CI, continuous infusion