Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12234
Peer-review started: May 8, 2015
First decision: August 31, 2015
Revised: September 5, 2015
Accepted: October 23, 2015
Article in press: October 26, 2015
Published online: November 21, 2015
Irinotecan hydrochloride is a camptothecin derivative that exerts antitumor activity against a variety of tumors. SN-38 produced in the body by carboxylesterase is the active metabolite of irinotecan. After irinotecan was introduced for the treatment of metastatic colorectal cancer (CRC) at the end of the last century, survival has improved dramatically. Irinotecan is now combined with 5-fluorouracil, oxaliplatin and several molecularly-targeted anticancer drugs, resulting in the extension of overall survival to longer than 30 mo. Severe, occasionally life-threatening toxicity occurs sporadically, even in patients in relatively good condition who have a low risk of chemotherapy-induced toxicity, often causing the failure of irinotecan-based chemotherapy. Clinical pharmacological studies have revealed that such severe toxicity is related to exposure to SN-38 and genetic polymorphisms in UDP-glucuronosyltransferase 1A1 gene. The large inter- and intra-patient variability in systemic exposure to SN-38 is determined not only by genetic factors but also by physiological and environmental factors. This review first summarizes the roles of irinotecan in chemotherapy for metastatic CRC and then discusses the optimal dosing of irinotecan based on the aforementioned factors affecting systemic exposure to SN-38, with the ultimate goal of achieving personalized irinotecan-based chemotherapy.
Core tip: Irinotecan is a key anticancer drug for the treatment of metastatic colorectal cancer. By combining irinotecan with 5-fluorouracil, oxaliplatin, and a molecularly-targeted drug, overall survival of longer than 30 mo has been achieved. Exposure to SN-38, the active metabolite of irinotecan, shows large inter- and intra-patient variability and can cause severe irinotecan-related toxicities. Many studies have recommended the dose reduction of irinotecan for patients with UDP-glucuronosyltransferase 1A1 polymorphisms and liver dysfunction. Surprisingly, dose reduction may be required in patients with severe renal failure, even though irinotecan is predominantly eliminated via the liver.