Biomarkers of skin toxicity induced by anti-epidermal growth factor receptor antibody treatment in colorectal cancer

Table 1 Previous studies which evaluated the predictive biomarker of severity of skin toxicity induced by anti- epidermal growth factor receptor antibody treatment in colorectal cancer

Ref.	Methods	Predictive markers	Risk factors of severe skin toxicity
Jatoi et al[39] (2009)	Patient's backgrounds	Age	Younger
		Gender	Men
Graziano et al[40] (2008)	EGFR polymorphism	CA repeat in EGFR intron-1	EGFR intron-1 S/S variant
Vallböhmer et al[42] (2005)	mRNA expression	Cox-2	Low expression
Takahashi et al[43,44] (2014, 2015)	Serum levels of ligands	AREG, EREG, HGF	Low levels of ligands at pre-treatment

EGFR: Epidermal growth factor receptor; Cox-2: Cyclo-oxygenase 2; AREG: Amphilegulin; EREG: Epiregulin; HGF: Hepatocyte growth factor.

Table 2 Skin toxicity as a biomarker of predicting the efficacy of anti-epidermal growth factor receptor antibody treatment in prospective phase II-III trial of unresectable colorectal cancer

Ref.	Number	Treatment	Clinical trial	Objective response rate		Overall survival
				Grade of skin toxicity	P value	Grade of skin toxicity (mo)	P value	HR (95%CI)
Jonker et al[45] (2007)	283	Cetuximab	Phase III	-	-	2.6 vs 4.8 vs 8.4 (grade 0 vs grade 1 vs≥ grade 2)	< 0.001	-
Van Cutsem et al[46] (2007)	200	Panitumumab + BSC	Phase III	14% vs 86% (grade 1 vs grade 2-3)	-	ND	-	0.59 (0.42-0.85)
Cunningham et al[4] (2004)	218	IRI + cetuximab	Phase III	6.3% vs 25.8% (grade 0 vs any grade)	0.005	3.0 vs 9.1 (grade 0 vs any grade)	-	-
	111	Cetuximab		0% vs 13.0% (grade 0 vs any grade)		2.5 vs 8.1 (grade 0 vs any grade)	-	-
Sobrero et al[47] (2008)	648	IRI + cetuximab (2nd-line)	Phase III	-	-	5.8 vs 11.7 vs 15.6 (grade 0 vs grade 1-2 vs≥ grade 3)	-	-
Bokemeyer et al[48] (2009)	169	FOLFOX + cetuximab (1st-line)	Phase II	13.0 vs 43.2% vs 53.2% vs 66.7% (grade 0 vs 1 vs 2 vs 3)	-	-	-	-
Stintzing et al[41] (2013)	149	CAPIRI/CapOX + cetuximab (1st-line)	Phase II	41% vs 62% (grade 0-1 vs grade 2-3)	0.021	18.0 vs 30.3 (grade 0-1 vs grade 2-3)	0.161	0.75 (0.50-1.12)

IRI: Irinotecan; ND: Not described; FOLFOX: 5-fluorouracil/leucovorin/oxaliplatin; CAPIRI: Capecitabine/irinotecan; CapeOX: Capecitabine/oxaliplatin; BSC: Best supportive care.