Research On The Safety Of Antineoplastic Drugs Based On Trigger And Data Mining

Objective:The trigger and data mining algorithm were used to analyse the adverse drug events(ADEs)of antineoplastic drugs through the hospital electronic medical record system and the United States Food and Drug Administration Adverse Event Reporting System(FAERS)database.To determine the characteristics of antineoplastic-induced ADEs in the real clinical settings for providing references in clinic.Methods:1.Summarizing and sorting the common ADRs of antineoplastic drugs through the instructions,literatures,and collecting the trigger items from relevant literatures to establish the initial trigger items.Ten clinical and pharmaceutical experts in the field of oncology were selected to consult on the importance of the initial triggers,and the final trigger was determined after discussion and modification.2.A random sample of 500 cancer inpatients in Chongqing cancer hospital discharged from January to December 2017,and a component medical record review team conducted a retrospective analysis.The positive predictive value(PPV),the incidence of ADEs,and the risk factors of serious adverse event(SAE)were evaluated.3.The proportional reporting ratio(PRR)data mining algorithm was used to detect signals of ADEs for erlotinib,sunitinib and bevacizumab from FAERS during 2004Q1-2018Q3.Results:1.The most common ADEs of antineoplastic drugs reported in literatures were gastrointestinal tract reaction(mucositis,diarrhea,constipation,nausea and vomiting),bone marrow suppression(anemia,neutropenia,thrombocytopenia),liver toxicity(aminotransferase abnormality),renal toxicity(elevated serum creatinine),peripheral nerve toxicity(paresthesia),skin toxicity(rash,hand-foot syndrome).2.Seven literatures on oncology-specific trigger tool were included,including four different versions of trigger tool,and 22 trigger items were extracted after preliminary screening.36 initial trigger items were determined based on the results of the previous survey on adverse reactions to antineoplastic drugs.After expert consultation and group discussion,33 trigger items were finally established,including 19 laboratory indicators,9 clinical symptoms,3 therapeutic drugs and 2 intervention measures.3.499 cases of qualified medical records were included for review.1 070 positive triggers were detected in 356 patients with 616 ADEs(4 duplicates).The PPV of the trigger tool was 57.94%,and the incidence of ADEs was 71.34%.83.27% of the ADEs were grade 1-2,16.88% of the ADEs were grade 3-4,and no injuries were identified as grade 5.Also,18.84% of the patients occurred SAE.ADEs were most frequently involved in the blood system(291,47.24%),followed by the gastrointestinal system(206,33.44%).There were 27 antineoplastic drugs related ADEs,cyclophosphamide(14.64%),paclitaxel(13.47%)and cisplatin(8.78%)appearing the most frequently.The duration of hospitalization,number of combination drug,and the history of adverse drug reaction were risk factors for SAE.4.A total of 19 855,16 379 and 43 214 of ADE reports were retrieved from FAERS for erlotinib,sunitinib and bevacizumab,respectively.Among which,more females than males(except for sunitinib),mainly aged in 45-64 years,and most adverse event outcomes were death and hospitalization.Skin toxicity were the most commonly ADEs for erlotinib,and 7 of the top 20 adverse events were related to it,especially rash(3 192).In addition to skin toxicity,bone marrow suppression,systemic reaction(fatigue,fatigue),and endocrine toxicity(hypothyroidism)were associated with sunitinib.By contrast,there are more vascular-related events(hypertension,pulmonary embolism,deep venous bleeding)for bevacizumab.Hemorrhage signals emerged for erlotinib,sunitinib,and bevacizumab,mainly involving the digestive tract,such as the stomach,intestine,and esophagus.It is worth noting that pulmonary hemorrhage,cerebral hemorrhage,subarachnoid hemorrhage,and retinal hemorrhage.In addition,the gastrointestinal perforation signals were found for the three agents,involving the stomach,large intestine,small intestine and other organs.The following perforation indicated the high signal intensity: corneal perforation(erlotinib,bevacizumab),nasal septum perforation(sunitinib,bevacizumab),esophageal perforation(bevacizumab).Conclusion:The incidence of adverse events of antineoplastic drugs is high,which can damage all systems or organs,bone marrow suppression and digestive tract reaction are the most frequently.Molecular targeted small-molecule anti-cancer drugs have a different adverse events spectrum from traditional chemotherapy drugs,with the same target drugs and similar adverse reactions.Active monitoring and passive monitoring have their own advantages in drug safety research.The combination of the two methods can make up for each other and help to comprehensively evaluate the safety of drug.