ObjectivesTo systematically review the risk of arterial ischemic and metabolic adverse events in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs).MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were searched to collect clinical trials, observational studies and case reports of adverse events in CML patients treated with TKIs from inception to February 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 12.0 software.ResultsA total of 22 studies involving 4 223 patients were included. The incidence rates of ischemic heart disease in any grade were 2 per 100 patient-years (95%CI 2 to 3) for nilotinib, and 0 per 100 patient-years (95%CI 0 to 3) for imatinib. The incidence of ischemic heart disease in grade 3 or 4 was 1 per 100 patient-years (95%CI 0 to 2) for nilotinib. The incidence of peripheral arterial occlusive disease in any grade was 2 per 100 patient-years (95%CI 0 to 14) for nilotinib, and 0 per 100 patient-years (95%CI 0 to 2) for imatinib. The incidence of hypertension in any grade was 1 per 100 patient-years (95%CI 0 to 3) for nilotinib, and 44 per 100 patient-years (95%CI 27 to 71) for ponatinib. The incidence of hypertension in grade 3 or 4 was 2 per 100 patient-years (95%CI 0 to 15) for nilotinib, and 22 per 100 patient-years (95%CI 8 to 58) for ponatinib. The incidence of hyperlipidemia in any grade was 17 per 100 patient-years (95%CI 5 to 59) for nilotinib. The incidence of hyperglycemia in any grade was 11 per 100 patient-years (95%CI 9 to 15) for nilotinib, 2 per 100 patient-years (95%CI 1 to 4) for imatinib, 1 per 100 patient-years (95%CI 0 to 5) for dasatinib, and 19 per 100 patient-years (95%CI 19 to 20) for bosutinib. The incidence of hyperglycemia in grade 3 or 4 was 4 per 100 patient-years (95%CI 3 to 5) for nilotinib, and 1 per 100 patient-years (95%CI 1 to 2) for bosutinib.ConclusionsPatients treated with nilotinib have a greater possibility of ischemic heart and peripheral arterial occlusive disease compared with patients treated with imatinib. Patients treated with ponatinib have a high incidence rate of hypertension, and patients treated with nilotinib have a high incidence rate of hyperlipidemia. Patients treated with bosutinib and nilotinib have higher risk of hyperglycemia compared with patients treated with imatinib or dasatinib.
ObjectiveTo systematically review the efficacy and safety of different tyrosine kinase inhibitors (TKIs) in the treatment of chronic myelocytic leukemia (CML).MethodsPubMed, EMbase, The Cochrane Library, CBM, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) of nilotinib, dasatinib, flumatinib and imatinib for CML from inception to August, 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; network meta-analysis was then performed using Stata 15.0 software and R 3.4.0 software.ResultsA total of 8 RCTs involving 2 775 patients were included. Compared with other TKIs, flumatinib had higher 3-month early molecular response and 1-year progression free survival, and the incidence of serious side effects was relatively low. Major molecular response and complete cytogenetic response were significantly superior to imatinib, and had the same or similar effects to other second-generation TKIs.ConclusionsCurrent evidence shows that flumartinib in the treatment of CML is obviously superior to imatinib, has the same or similar effect with other second generation TKIs. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusions.
ObjectiveTo systematically review the renal adverse reactions of tyrosine kinase inhibitors (TKI). MethodsPubMed, EMbase, Cochrane Library, CNKI, WanFang Data and CBM databases were electronically searched to collect randomized controlled trials (RCTs) on the incidence of renal adverse reactions of TKI from inception to March 30, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4 software. ResultsA total of 19 RCTs involving 10 141 patients were included. The results of meta-analysis showed that compared with placebo or blank control, gefitinib, ranvartinib, cabotinib, vandetanib, pazopanib, arotinib, apatinib, and acitinib could lead to an increased risk of proteinuria events, while sildenib did not increase the risk of proteinuria in patients. Anlotinib could increase the risk of hematuria. Vandetanil increased the risk of acute kidney injury. Gefitinib, ranvartinib and apatinib could increase the risk of grade 3-4 renal adverse reactions. ConclusionCurrent evidence shows that TKI drugs may cause renal damage in patients, and proteinuria is the most common. Vandetanil can cause acute kidney injury, gefitinib, ranvartinib and apatinib are more nephrotoxic. The renal adverse reactions of neratinib, ibutinib and sildenib are relatively few.