Optimum patient selection for irinotecan-containing regimens in metastatic colorectal cancer: Literature review and lessons from clinical practice.

Metastatic colorectal cancer (mCRC) accounts for over 20% of CRC cases and is associated with a poor prognosis. Irinotecan is an important first- and second-line chemotherapy option for mCRC. In this review, we summarize the clinical efficacy and safety of irinotecan-based regimens for the treatment of mCRC and discuss various tumor- and patient-related factors that affect the clinical response, survival, and toxicity associated with these regimens. Uridine diphosphate glucuronosyltransferase (UGT) gene polymorphisms such as UGT1A1*28/*6, age, performance status, serum lactate dehydrogenase levels, and bilirubin levels could be important considerations for predicting outcomes and tolerability with irinotecan-based regimens. The role of tumor location; chemotherapy backbone; and emerging evidence on the presence of microsatellite instability-high status, consensus molecular subtype 4 tumors, and signet-ring morphology in predicting response to irinotecan-based therapy have also been highlighted. Careful consideration of these factors will help guide clinicians in optimizing the selection of mCRC patients for irinotecan-based treatment.