Multi-factor Analysis On The Clinical Efficacy And The Prognosis Of Anlotinib

Background and Objective:Apoptosis disorder,DNA damage and abnormal blood vessel growth are the main causes of tumor occurrence,development and metastasis.The growth and proliferation of tumor cells require nutrients and oxygen,both of which are derived from blood vessels.Blood vessels are the basic condition for supporting tumor survival,and are also important conditions for tumors to infiltrate adjacent tissues and distant metastases.Folkman said that blocking blood vessels was an important means of inhibiting tumor growth infiltration and distant metastasis.Angiogenesis-related factors,such as VEGF,PDGF,FGF,etc.,which play vital roles in the process of neovascularization.With the in-depth exploration and research of various anti-tumor theories,anti-angiogenesis drugs represented by Endo,Bevacizumab,Ramulizumab,Apatinib,etc.have been widely used in clinical practice and have achieved significant effects.And many studies found that the expression of some vascular related factors was related to the efficacy of anti-angiogenic drugs;the expression of c-Kit,Bcl-2 and DNA damage repair enzyme PARP might also be related to the anti-tumor efficacy.Anlotinib is a new type of angiogenesis inhibitor.Existing research shows that it can clinically benefit patients with tumors of multiple tumor types.The purpose of this study is to observe the relevant indicators of patients with malignant tumors of multiple tumor types treated with anlotinib,and to initially explore the factors that affect the clinical efficacy and prognosis of anlotinib.Methods:(1)Patients with advanced malignant tumors who were hospitalized in the Department of Oncology,Affiliated Hospital of Guilin Medical University from July 2018 to December 2019 were selected.The treatment plan was anlotinib monotherapy or anlotinib combined with others.Collect clinical features,evaluate patients'disease control rate and objective response rate according to relevant review data,follow up and record adverse reactions(including clinical manifestations,signs and hematology examinations)and progression-free survival(PFS)during treatment process.(2)Blood was collected from the patients during treatment on an empty stomach,and serum VEGF,FGF,SCFR,Bcl-2 and PARP content were detected by ELISA;relative expression of VEGF m RNA,c-Kit m RNA,Bcl-2 m RNA and PARP m RNA were detected by q RT-PCR.(3)Measurement data were expressed as mean±standard deviation,count data were expressed as the number of cases and percentages.Chi-square test was used for comparison between groups;Kaplan-Meier method was used to make survival curves,and Log-rank test was used to compare the differences between survival curves;Single factor analysis,multivariate logstic regression analysis and Cox regression multivariate analysis were performed on the related factors affecting clinical efficacy and prognosis.P<0.05 indicates that the difference is statistically significant.Results:Follow-up was completed on December 2,2019,a total of 109patients with advanced malignant tumors were collected.Eight patients were excluded because they did not return to hospital for review and could not evaluate the efficacy.101 patients were included in the study.The total median PFS was 4.8 months(95%CI:3.824-5.776).Among the evaluable cases,0 case were CR(0.00%),18 cases were PR(17.82%),61 cases were SD(60.40%)and22 cases were PD(21.78%).A total of 79 cases achieved disease control,with a total DCR of 78.22%,and 18 cases achieved objective remission,with a total ORR of 17.82%.Treatment-related adverse reactions were:6 cases of hypertension(5.94%),7 cases of hand-foot syndrome(6.93%),4 cases of oral ulcers(3.96%),4 cases of fatigue(3.96%),and 2 cases of hoarseness(1.98%),6cases of cough(5.94%),4 cases of hemoptysis(3.96%),6 cases of bloating and diarrhea(5.94%),1 case of urine leakage(0.99%),1 case of vaginal bleeding(0.99%),16 cases of bone marrow suppression(15.84%),transaminase increased in 17 cases(16.83%),blood lipid increased in 10 cases(9.90%),thyroid stimulating hormone(TSH)increased in 17 cases(16.83%),most of them were grade 1-2,1 case hypertension was grade 3,1 case bone marrow suppression(thrombocytopenia)was grade 4,and no drug-related death.Chi-square test results showed that patients with increased TSH had higher DCR than those who did not(P=0.039).Logistic regression analysis suggested that combination medication(P=0.030)could be an independent influencing factor for improving disease control rate,and it was a protective factor.However,the occurrence of bone marrow suppression cannot be an independent factor of DCR(P>0.05).The chi-square test showed that patients with a history of disease-related surgery had a higher ORR than patients without disease-related surgery(P=0.047).Logistic regression analysis suggested that no related factors could be used as independent factors of ORR(P>0.05).Kaplan-Meier method was used for survival analysis.Log-Rank test analysis of relevant clinical data,the median PFS of patients with clinical stage III was significantly longer than that in stage IV(11.4 months vs 4.2 months,x~2=4.253,P=0.039),and patients who had used platinum had a longer median PFS than those who did not(5.3 months vs 3.6 months,x~2=4.299,P=0.038).Log-Rank test was used to analyze treatment-related adverse reactions.The median PFS of patients with increased TSH was longer than those who did not(6.4 months vs 4.0months,x~2=3.982,P=0.046),and the median PFS of patients with hand-foot syndrome was also longer than those who did not(11.4 months vs 4.2 months,x~2=5.297,P=0.021).Univariate analysis of clinical features,treatment-related adverse reactions,serum content and relative expression of m RNA of each factor.The results showed clinical stages,previous platinum use history,hand-foot syndrome,TSH increased,serum b FGF content,the relative expression of Bcl-2 m RNA and PARP m RNA were the factors affecting the prognosis of patients.The above factors were incorporated into the Cox regression equation,and the results showed that the serum b FGF content(P=0.009)and the relative expression of Bcl-2 m RNA(P=0.012)were independent factors affecting the prognosis of anlotinib in the treatment of advanced malignant tumors.Conclusions:(1)This study shows that patients with various advanced malignant tumors have different degrees of clinical benefit with anlotinib treatment,and adverse reactions can be tolerated.(2)Serum b FGF content and relative expression of Bcl-2 m RNA are independent factors affecting the prognosis of patients treated with anlotinib.Detecting the expression of the above two indicators during treatment may help predict the prognosis.(3)The efficacy of anlotinib may be better in patients who use the combined regimen and have adverse effect of thyrotropin elevation,The question"Anlotinib+?"that will benefit patients more needs to be explored in clinical work.(4)Early clinical stage,used platinum,the occurrence of hand-foot syndrome and elevated thyrotropin may indicate a better prognosis for patients treated with anlotinib.(5)This study preliminarily determined the effectiveness and safety of anlotinib in the treatment of other tumor types(such as liver cancer,ovarian cancer,head and neck cancer,pancreatic cancer,tongue cancer,etc.),and provided a reference for the selection of subsequent treatments.(6)This study has initially explored the factors affecting the clinical efficacy and prognosis of anlotinib,and it is worthy of further expansion of the clinical sample size in a single disease.