| Irinotecan is a DNA topoisomerase I inhibitor that acts on the S phase of the cell cycle and prevents the repair of DNA strand breaks by topoisomerase I,inhibition of cell division exhibits anticancer activity.Irinotecan has been widely used in the treatment of solid tumors such as colorectal cancer,non small cell carcinoma and gastric cancer.However,it is limited in clinical application due to the severe adverse reactions such as bone marrow suppression and delayed diarrhea.There were significant differences in the incidence of adverse reactions of irinotecan.The toxicity of irinotecan chemotherapy related UGT1A1 gene polymorphism,drug dose and irinotecan,the purpose of this study was to observe the correlation of clinical application with irinotecan chemotherapy adverse reactions in patients with malignant tumor and curative effect with UGT1A1 *28,UGT1A1 *6,dose of clinical factorsFifty-one blood samples of the patients with malignancy treated with irinotecan in medical oncology department of the Fiesta Affiliated Hospital of Hebei North University from Dec.2013 to Aug.2016 were collected.All specimens were tested for UGT1A1*28 and UGT1A1*6 locus.After the patients were enrolled in the study,the side effects of the patients were observed and the therapeutic effect was evaluated periodically.The plasma sample was determined by HPLC-flurorescence method after protein with acetonitrile.The determination was performed on Waters C18 column with mobile phase consisted of 0.05 mol·L-1 sodium dihydrogen phosphate-acetonitrile(70:30,V/V,pH adjusted to 4.0 using phosphoric acid)at the flow rate of 1.0 ml·min-1.The excitation wavelength was set at 380 nm.The emission wavelengths of irinotecan and its active metabolites were set at 480 nm and 535 nm,respectively.The column temperature is 25 ℃and the injection volume is about 20 μL.To determine the concentration of SN-38 in patients,and to explore its correlation with adverse reactions and curative effectIn 51 patients,TA6/TA6 normal wild type in 40 cases(78.4%),TA6/ TA7 heterozygous mutation in 10 cases(19.6%),1 cases of variation TA7/7 homozygous mutation(1.2%);G/G normal wild type in 36 cases(70.5%),15 cases of variation G/A heterozygous mutation(29.5%),0 cases of homozygous mutant A/A(0%).51 cases of tumor patients,15 cases had delayed diarrhea,12 cases of degree 1-2 with mild adverse reactions,3 cases of degree 3-4 severe adverse reactions;42 cases occurred in patients with Neutropenia,30 cases of degree 1-2 mild adverse reactions,12 cases of degree 3-4 severe adverse reaction.Single factor analysis showed that the adverse reactions were not related to the general clinical factors,diarrhea is associated with UGT1A1 *28 gene mutations and neutropenia is associated with UGT1A1 *6 gene mutations.To avoid confounding factors can be evaluated after the efficacy of 41 patients,including CR,,PR,SD18,,PD21 cases,the effective rate was 23.5%(6/26);disease control rate was54.9%.There was no significant difference in gene polymorphism,serum concentration and short-term efficacy.The peak concentration of SN-38 was 23.4 ng·mL-1,and the peak concentration of SN-38 had no significant correlation with adverse reactions and short-term efficacy.In conclusion,UGT1A1 *28 gene mutation is a risk factor for the occurrence of delayed diarrhea.UGT1A1 *6 mutation and the initial dose is a risk factor for neutropenia,UGT1A1 and *6 gene mutation in patients with 3-4 can increase the risk of severe neutropenia;UGT1A1 *28 mutation,UGT1A1 mutation,*6 dose and short-term curative effect;active metabolite SN-38 peak concentration and delay diarrhea,neutropenia,recent independent. |
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