Single-center Observational Study Of Adverse Drug Reaction Of Apatinib Utilized In Malignant Tumor Therapy

BackgroundMalignancy makes serious damage to human health.The incidence and mortality increase by years worldwide,raising concerns about tumor therapy.Tumor therapy shoud be multi-disciplinary combined therapy.Nowadays,the theraputic method of maglinancy mainly contains surgical treatment,medical treatment,radiotherapy,interventional therapy,and so on.However,the available theraputic method can not meet the clinical demand.Anti-tumor targeted drugs have get great breakthrough and huge benifits for the past decade,raising a new hope for tumor therapy.Targeted therapy can supress the growth and migrancy of tumors by directly playing action on tumor-related molecules,which play a role in the process of cellular signal transduction.Compared with traditional cytotoxic chemotherapy,targeted therapy are more targeting and accurate to tumor cell,reducing effectiveness to normal cell,which is benificial to individual therapy.According to the actional machanism,targeted drugs can be classified to two types:small molecule inhibitors and monoclonal antibodies.Apatinib mesylate is a molecule tyrosine-kinase inhibitor approved for marketing by CFDA in the year 2014,applying to the third line or post-third line therapy of advanced gastric or gastroesophageal adenocarcinoma.The mechanism of apatinib is high selectively inhibiting VEGFR-2 tyrosine kinase,blocking the intracellular signal transduction,sothat supressing tumor angiogenesis,finally supressing tumor growth.Clinical experiments before approved for maketing showed that apatinib has well effectiveness and safety.The incidence rate of severe adverse drug reaction is low.At pressent,several clinical experiments about apatinib using for other kinds of carcinoma are carried out.In the clinical work,apatinib has been applied to many carcinomas besides gastric carcinoma in some cases.ObjectivesTo observe and research the safety of apatinib furtherly.To explore the correlation of some SNPs polymorphysm(CYP3A4*1B?CYP3A5*3?CYP2C9*3)with the incidence of adverse drug reaction of apatinib.MethodsCollecting and analyzing the clinical information of patients who have used apatinib for maglinancy in Qilu hospital of Shandong University between 2014.6-2014.12.The information contains name,sex,age,disease,therapy line,ECOG score,drug dossage.Mornitoring the adverse reaction of apatinib by telephone follow-up and other ways.Grading the drug adverse reaction according to CTCAE4.03.Inclusion criteria:malignant carcinoma which was vertified by pathology;using apatinib for monotherapy;no obvious abnormity in blood routine and important organ function.Exclusion criteria:using apatinib for less than 10 days;didn't test blood routine or hepatorenal function after using apatinib.For patients who have suffered severe adverse drug reaction,draw the vein blood to test the polymorphysm of CYP3A4*1B?CYP3A5*3?CYP2C9*3,with the agreement of patients.Adopt SPSS17.0 for statistical analysis.Multivariate analysis:logistic-regression;comparison among groups:Chi-square test.P<0.05 is defined meaningful.Results1.Basic information49 patients were included.14 lung cancer,9 gastric carcinoma,6 ovarian cancer,4 colorectal cancer,4 breast cancer,3 sarcoma,2 esophagus cancer,2 duodenal cancer,pancreatic cancer,2 biliary duct cancer,1 gingival cancer.24 male,25 female.The median age is 53-year-old.ECOG score:17patients were 0,19 patients were 1,13 patients were 2.About therapy line:20 patients were less than the third line,29 were for the third line or post-third line.The initial dossage:5 patients were 250mg qd,2 patients were 425mg qd,32 patients were 500mg qd,6 patients were 675mg qd,4 patients were 850mg qd.2.Statistics of adverse drug reactionThe incidence rate of adverse reaction was 100%,while the severe adverse reaction was 59.2%.The five leading ADR were:hypertension(57.1%),hand-foot syndrome(42.9%),decreased appetite(42.9%),fatigue(40.80%),proteinuria(37.1%).The four leading severe ADR were:hypertension(32.7%)?hand-foot syndrome(12.2%)?stomatitis(8.2%)?diarrhea(8.2%).The incidence of severe ADR was related with location of the tumor.There was a higher rate in cancer of digestive system than in non-digestive system(x2=5.408,P<0.05).While,severe ADR was not related with other factor.The incidence of Severe hypertension has a negative relationship with ECOG score.The incidence of severe hand-foot syndrome had no relationship with the statistical factors.3.SNPs polymorphismThe SNPs polymorphism of CYP3A4a*1B?CYP3A5*3?CYP2C9*3 were tested in 9 patients.The gene frequency of CYP3A4*1B was 0%,CYP3A5*3 was 75%,CYP2C9*3 was 0%.Conclusions1.The incidence of ADR and severe ADR of apatinib are relatively high,with the priority of hypertension and hand-foot syndrome.2.There is a higher incidence rate in cancer of digestive system than in non-digestive system.3.The incidence of Severe hypertension has a negative relationship with ECOG score.4.The incidence of severe ADR probably has no correlation with the SNP polymorphism of CYP3A4*1B?CYP3A5*3?CYP2C9*3.