Table 3.

Evidence base in support of exposure–response–toxicity for 5-FU.

Study details	Disease	Pk parameter	Exposure–toxicity	Exposure–clinical response
Hillcoat (1978) (67) (original study)	GI malignancies	AUC	Not reported	RR with TDM: 40% RR without TDM: 5%
Thyss (1986) (68) (original study)	Head and neck cancer	AUC	Strong relationship	Good response rate
van Groeningen (1988) (69) (original study)	Advanced malignancies	AUC	Strong relationship	Not Available
Fety (1998) (70) (original study)	Head and neck cancer	AUC	Reduced adverse events	Good response rate RR with TDM: 18% RR without TDM: 8%
Gamelin (2008) (71) (original study)	mCRC	AUC	Strong relationship	Not Available
Yoshida (2008) (72) (original study)	mCRC	AUC	Strong relationship	Not Available
Wilhelm (2016) (73) (original study)	mCRC	AUC	Decreased toxicities	RR with TDM: 20% RR without TDM: 12%
Yang (2016) (74) (original study)	Colorectal cancer	AUC		Superior overall response rate
Fang (2016) (75) (original study)	Solid tumors	AUC	Lower the probability of grade 3/4 adverse drug events	Superior overall response rate
Salamone (2017) (76) (original study)	mCRC	AUC	Less rates of grade 3/4 adverse events	Good response rate
Deng (2020) (77) (original study)	mCRC	AUC	Incidence of adverse events reduced	Long-term efficacy improved

This is a nonexhaustive list, including only the important, landmark studies that led to the consensus for adoption of 5-FU TDM.