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Copyright ©The Author(s) 2015.
World J Gastroenterol. Nov 21, 2015; 21(43): 12234-12248
Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12234
Table 1 Representative phase III clinical trials evaluating first-line chemotherapies in patients with metastatic colorectal cancer
Trials (primary endpoint)RegimensOverall survival (OS) (mo)P valueProgression-free survival (PFS) (mo)P valueResponse rate (RR)P valueRef.
0038 (PFS)5-FU/LV12.60.0404.30.00421%< 0.001[33]
V303 (RR)5-FU/LV14.10.0314.4< 0.00122%< 0.005[34]
(PFS)5-FU/LV14.70.1206.2< 0.00122.3%< 0.001[35]
V308 (2nd PFS)1FOLFIRI→FOLFOX621.50.9908.50.26056%> 0.05[39]
GONO (RR)FOLFIRI16.70.0326.90.00141%< 0.001[40]
NO16966 (PFS)FOLFOX/CapeOX19.90.0778.00.00249%0.310[45]
FOLFOX/CapeOX + Bev21.39.447%
CRYSTAL (PFS)FOLFIRI18.60.3108.00.04838.7%0.004[42]
FOLFIRI + Cet19.98.946.9%
PRIME (PFS)FOLFOX19.70.0728.00.02048%0.068[46]
FOLFOX + Pan23.99.655%
FIRE-3 (PFS)FOLFIRI + Bev25.00.01710.30.55058%0.180[44]
FOLFIRI + Cet28.710.062%
TRIBE (PFS)FOLFIRI + Bev25.80.0549.70.00353.1%0.006[3]
FOLFOXIRI + Bev31.012.165.1%
Table 2 Factors affecting SN-38 exposure and dosage recommendation of irinotecan summarized in this review
FactorsExposure to SN-38Irinotecan-induced toxicityDosage recommendationRef.
Pharmacogenetic factors
UGT1A1*6 and *28AUC ↑Severe neutropenia (diarrhea)↑Need to be reduced (prescription information in the US and Japan etc.)[10-13,53,54,59,60]
SLCO1B1*15AUC ↑Severe neutropenia↑No recommendation exists (need to be reduced?)[62-64,67]
Physiological factors
Age (elderly patients)Comparable to youngerComparable to youngerNo need to be modified[82,87-89]
Body size (obesity)Similar in BSA-based and flat-fixed dosingSimilar in BSA-based and flat-fixed dosingNo need to be modified (flat-fixed dosing)[48,54,68]
Organ dysfunctions
LiverAUC ↑Severe neutropenia (diarrhea)↑Need to be reduced[95-97]
KidneyAUC ↑Mild to moderate, but prolonged neutropeniaProbably need to be reduced[101,103]
GenderLower in female?Severe hematologic toxicity in female?No recommendation exists[8,65,88,112,113]
Environmental factors
Medication (drug-drug interactions)No data availablePolypharmacy-related toxicityNo recommendation exists[114]
Life style
SmokingAUC ↓Lower toxicityNo recommendation exists[115]