Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer: A critical update

Table 1 Oral mucositis grading scales

CTCAE version 4.03	Grade
	1	2	3	4	5
Description	Asymptomatic or mild symptoms; intervention not indicated	Moderate pain; not interfering with oral intake; modified diet indicated	Severe pain; interfering with oral intake	Life-threatening consequences; urgent intervention indicated	Death
WHO	Grade
	0 (none)	I (mild)	II (moderate)	III (severe)	IV (life-threatening)
Description	None	Oral soreness, erythema	Oral erythema, ulcers, solid diet tolerated	Oral ulcers, liquid diet only	Oral alimentation impossible

CTCAE: Common Terminology Criteria for Adverse Events version; WHO: World Health Organization.

Table 2 Frequency of gastrointestinal toxicities in metastatic colorectal cancer: results from main recent clinical trials

Trials	Nausea		Vomiting		Diarrhea		Oral mucositis
	Any grade	G3-G4	Any grade	G3-G4	Any grade	G3-G4	Any grade	G3-G4
Folfiri + cetuximab (FIRE-3 trial, Heinemann et al[12]. Lancet Oncol 2014)	45%	3%	22%	2%	46%	11%	38%	4%
Folfiri + bevacizumab (FIRE-3 trial, Heinemann et al[12]. Lancet Oncol 2014)	58%	5%	29%	3%	49%	12%	41%	3%
Folfiri + aflibercept (VELOUR trial, Van Cutsem et al[60]. J Clin Oncol 2012)	53.4%	1.8%	32.9%	2.8%	69.2%	19.3%	54.8%	13.8%
Regorafenib (CORRECT trial, Grothey et al[63]. Lancet 2013)	14%	< 1%	8%	1%	34%	7%	27%	3%
Folfoxiri + bevacizumab (Tribe trial, Loupakis et al[13]. N Engl J Med 2014)		2.8%		4.4%		18.8%		8.8%
Folfox + bevacizumab (Tribe trial, Loupakis et al[13]. N Engl J Med 2014)		3.2%		3.2%		10.6%		4.3%

Table 3 Frequency of gastrointestinal toxicities in advanced pancreatic cancer: results from main clinical trials

Trials	Nausea		Vomiting		Diarrhea		Oral mucositis
	Any grade	G3-G4	Any grade	G3-G4	Any grade	G3-G4	Any grade	G3-G4
Gemcitabine + TH-302 (240 mg/m2) (Borad et al[78]. J Clin Oncol 2014)	39%	10%	24%	6%	28%	3%	18%	0%
Gemcitabine + TH-302 (340 mg/m2) (Borad et al[78]. J Clin Oncol 2014)	46%	5%	38%	8%	36%	4%	36%	0%
Sunitinib (Yao et al[81]. N Engl J Med 2011)	45%	1%	34%	0%	59%	5%	22%	4%
Everolimus (Raymond et al[84]. N Engl J Med 2011)			15%	0%	34%	3%	64%	7%
Folfirinox (PRODIGE 4/ACCORD11 trial, Conroy et al[71]. N Engl J Med 2011)				14.5%		12.7%
Nab-paclitaxel + gemcitabine (MPACT trial, Von Hoff et al[74]. N Engl J Med 2013)						6%