Correlative analysis of plasma SN-38 levels and DPD activity with outcomes of FOLFIRI regimen for metastatic colorectal cancer with UGT1A1 *28 and *6 wild type and its implication for indidualized chemotherapy.

Correlative analysis of plasma SN-38 levels and DPD activity with outcomes of FOLFIRI regimen for metastatic colorectal cancer with UGT1A1 *28 and *6 wild type and its implication for indidualized chemotherapy.

Cancer Biol Ther. 2017 Feb 17;:0

Authors: Cai X, Tian C, Wang L, Zhuang R, Zhang X, Guo Y, Lu H, Wang H, Li X, Gao J, Li Q, Wang C

Abstract
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 49 hour 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 > 50.24 g/ml subset was remarkably longer than that of the CSN-38 1.5h ≤ 50.24 g/ml subset. However, there were no differences between the CSN-38 49h > 15.25 g/ml subgroup and the ≤15.25 g/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 > 50.24 g/ml and CSN-38 49h > 15.25 g/ml subsets. Therefore, plasma SN-38 levels is related to outcomes for UGT1A1 *1/*1-*1/*1 genotype, in order to improve efficacy, patients with CSN-38 1.5h lower than 50.24 g/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.

PMID: 28278081 [PubMed - as supplied by publisher]

http://ift.tt/2mqvNLg