Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer

Table 2 Factors affecting SN-38 exposure and dosage recommendation of irinotecan summarized in this review

Factors	Exposure to SN-38	Irinotecan-induced toxicity	Dosage recommendation	Ref.
Pharmacogenetic factors
UGT1A1*6 and *28	AUC ↑	Severe neutropenia (diarrhea)↑	Need to be reduced (prescription information in the US and Japan etc.)	[10-13,53,54,59,60]
SLCO1B1*15	AUC ↑	Severe neutropenia↑	No recommendation exists (need to be reduced?)	[62-64,67]
Physiological factors
Age (elderly patients)	Comparable to younger	Comparable to younger	No need to be modified	[82,87-89]
Body size (obesity)	Similar in BSA-based and flat-fixed dosing	Similar in BSA-based and flat-fixed dosing	No need to be modified (flat-fixed dosing)	[48,54,68]
Organ dysfunctions
Liver	AUC ↑	Severe neutropenia (diarrhea)↑	Need to be reduced	[95-97]
Kidney	AUC ↑	Mild to moderate, but prolonged neutropenia	Probably need to be reduced	[101,103]
Gender	Lower in female?	Severe hematologic toxicity in female?	No recommendation exists	[8,65,88,112,113]
Environmental factors
Medication (drug-drug interactions)	No data available	Polypharmacy-related toxicity	No recommendation exists	[114]
Life style
Smoking	AUC ↓	Lower toxicity	No recommendation exists	[115]

AUC: Area under the plasma concentration-time curve.