The Clinical Analysis Of The Efficacy And Safety Of FOLFIRI Scheme As Second-line Treatment For Advanced Gastric Adenocarcinoma

Background: China is area that has a high incidence and mortality of gastric cancer,accounted for about40%of the world. Either the morbidity or mortality are highest in the topthree of malignant tumors, affecting the health and life of our people seriously. Advancedgastric cancer (AGC) accounts for80%of all gastric cancer. Chemotherapy is the primarytreatment of AGC, if the first line treatment failured, the physical state,treatment willstrongly patients face second-line therapy. NCCN guide no second-line treatment standard. Inaddition, the polymorphism of the UGT1A1gene may influence the toxicity of irinotecanrelated, some scholars believed that the UGT1A1*6and UGT1A1*28mutant increased theincidence of neutropenia and diarrhea.Objective: To compare the efficacy and toxicity of second chemotherapy with irinotecanplus fluorouracil and paclitaxel combined with fluorouracil in patients with AGC, whoreceived platinum as first-line treatment and failured, as well as the correlation betweenUGT1A1gene polymorphism and the toxicity of irinotecan. To discuss the feasibility ofirinotecan dose adjustments accorded to the detection results of UGT1A1genepolymorphism, hoping to enhance the irinotecan drug safety.Methods: Irinotecan combined with fluorouracil and paclitaxel plus fluorouracil foradvanced gastric adenocarcinoma of second-line treatment,tested the UGT1A1*28and UGT1A1*6genotype，analysised the correlation between UGT1A1gene polymorphismand the toxicity of irinotecan．Results:1.The irinotecan plus fluorouracil group25example，CR1example，PR4example，SD7example， PD13example, the calculated RR was20%, DCR was48%. Thepaclitaxel plus fluorouracil group23example,CR0example, PR4example, SD5example, PD14example, calculated the RR was17.4%, the DCR is39.1%. Two groups ofRR, DCR (P>0.05), no statistical significance. The median PFS of two groups were3.5months and2.5months, P <0.05, with statistical significance. The median OS were7.6months and6.8months, respectively,no statistical significance.2.72cases of patients usedirinotecan, UGT1A1*6genotype were G/G, G/A and A/A,and the incidence of grade3-4neutropenia were15.1%、43.8%、66.7%,, and grade3-4diarrhea rate were9.4%、25.0%、 66.7%, with statistical significance. Grade3-4neutropenia rates of UGT1A1*28genotypeTA6/6, TA6/7were16.4%、42.9%、66.7%, and the incidence of grade3-4diarrhea were7.3%、35.7%、66.7%, with statistical significance. Toxicity:(1) Hematological toxicity:Grade3-4neutropenia rates of irinotecan group and paclitaxel group were24%,30.4%, the incidence anemia were32.0%,30.4%, grade3-4platelet decline rates were12.0%,17.4%, P>0.05, no statistical significance.(2)Non hematological toxicity:Theincidence of diarrhea, nausea and vomiting of irinotecan group were28.0%and36.0%,paclitaxel group were4.3%,8.6%, the difference was statistically significant; The incidenceof muscle and joint pain,alopecia of paclitaxel group was34.8%, while irinotecan groupwas4%and8%, with statistical significance. Other adverse reactions as liver and kidneydamage, peripheral neuritis were no significant differences between them.Conclusion:(1) Schemes containing Irinotecan and paclitaxel there were no significantdifference in the efficacy. Adverse reactions of the two groups could be tolerated. Paclitaxelscheme was better tolerated. They could become the advanced options gastric cancer assecond-line treatment.(2) UGT1A1*6and UGT1A1*28mutant increased the incidence ofgrade3-4neutropenia and diarrhea, and can be used as a predictor for the toxicity ofirinotecan. Adjusted the irinotecan dose according to the results of the genetic test,reducedthe toxicity, to provide the basis for clinical individualized medication. According tothe genetic test results to adjust the irinotecan dose was feasible, can improve thesafety,,provided the basis for clinical individual therapy.