It remains uncertain whether there is an correlation between clinical pharmacokinetic parameters and outcomes for metastatic colorectal cancer especially with UGT1A1 *28 and *6 wild type (*1/*1-*1/*1) for serious events associated with Irinotecan are largely excluded. This study retrospectively analyzed the relationship between Irinotecan metabolite levels and outcomes of UGT1A1 *1/*1-*1/*1 genotype arrangement. Blood samples (n = 244) were collected for analysis of plasma DPD activity (before first chemotherapy) and SN-38 levels (1.5 and 49hour after CPT-11 administration). Clinical variables such as toxicity and outcomes were then assessed. Of the *1/*1 -*1/*1 genotype combination, the median progression free survival of the CSN-38 1.5h > 50.24ng/ml subset was remarkably longer than that of the CSN-38 1.5h 50.24ng/ml subset. However, there were no differences between the CSN-38 49h > 15.25ng/ml subgroup and the 15.25ng/ml group. It was lower DPD activity that responsible for the relatively higher incidence of bone marrow hypocellular, diarrhea, and oral mucositis in the CSN-38 1.5h > 50.24ng/ml and CSN-38 49h > 15.25ng/ml subsets. Therefore, plasma SN-38 levels is related to outcomes for UGT1A1 *1/*1-*1/*1 genotype, to improve efficacy, patients with CSN-38 1.5h lower than 50.24ng/ml, CPT-11 dosage could be added in next chemmotherapy on SN-38 plasma level monitoring. Additionally, in patients with DPD activity below 3.18 before treatment, appropriate reduction of 5-FU dose could be considered to minimize the incidence of adverse events.
[1]Nanjing Med Univ, Shanghai Gen Hosp, Dept Oncol, Shanghai, Peoples R China.
[2]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Oncol, Sch Med, Shanghai, Peoples R China.
[3]Peoples Hosp Guizhou Prov, Dept Nucl Med, Guiyang, Peoples R China.
[4]Fudan Univ, Shanghai Med Coll, Zhongshan Hosp, Dept Oncol, Shanghai, Peoples R China.
[5]Fudan Univ, Shanghai Med Coll, Dept Med Oncol, Shanghai Canc Ctr, Shanghai, Peoples R China.
[6]Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Tradit Chinese Med, Med Coll, Shanghai, Peoples R China.
[7]Shanghai Jiao Tong Univ, Renji Hosp, Dept Oncol, Med Coll, Shanghai, Peoples R China.
[8]Shanghai Tongji Univ, Shanghai Peoples Hosp 10, Dept Oncol, Shanghai, Peoples R China.
[9]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Clin Pharm, Sch Med, Shanghai, Peoples R China.
[10]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Radiotherapy, Sch Med, Shanghai, Peoples R China.
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