Relevant Clinical Studies Of Sorafenib For Targeted And Adjuvant Therapy Of Renal Cell Carcinoma

Renal cell carcinoma(RCC)is the most common malignant disease of the kidney.Sorafenib is a tyrosine kinase inhibitor(TKIs)that can inhibit the VEGF receptor and PDGF-β receptor.It is a first-line medicine for metastatic renal cell carcinoma(mRCC).But many patients still do not benefit from it,and there are still problems such as lack of prognostic markers,many adverse events,and a controversy over the efficacy of adjuvant therapy.Therefore,this study collects clinical data of RCC patients who have undergone targeted therapy and adjuvant therapy with sorafenib in our center,and conducts follow-up observations.Through retrospective studies,we explore the relationship between the efficacy and adverse events of sorafenib in the treatment of metastatic renal cell carcinoma.And explore the efficacy of sorafenib in adjuvant treatment of patients with non-metastatic renal cell carcinoma and analysis of factors related to tumor recurrence Objective: 1.To explore the relationship between the adverse events and efficacy of sorafenib in patients with metastatic renal cell carcinoma(mRCC).2.To explore the efficacy of sorafenib in postoperative adjuvant treatment for patients with non-metastatic renal cell carcinoma and the factors related to renal cell carcinoma recurrence.Methods: 1.A retrospective study of 63 patients with mRCC treated by sorafenib in Xijing Hospital was implemented.Analysis of the correlation between the tumor response rate and the frequency and severity of the adverse events by Chi-square test.The Kaplan-Meier method was used to analyze the adverse events.The adverse events relatedto PFS and OS were screened out,and the P<0.05 variable was included in the multivariate Cox proportional hazard regression model for further multivariate analysis to determine independent prognostic factors.2.A retrospective study was implemented for patients undergoing renal cancer resection at Xijing Hospital from October 2010 to August 2018.The sorafenib group(n =52)received oral sorafenib for 3 months after nephrectomy,and the control group(n = 52)received the same surgery without sorafenib therapy.The control group matched 1: 1 with sorafenib in terms of gender,age,pathological type,TNM staging and classification,and type of surgery.The disease-free survival(DFS)was observed as main endpoint.Kaplan-Meier was used for survival analysis.Chi-square test was used to analyze tumor recurrence rate and recurrence-related factors.Logistic regression analysis was used to further analyze tumor relapse-related factors.Results: 1.Among 63 patients who underwent sorafenib therapy,2 cases(3.2%)had complete response(CR),16 cases(25.4%)had partial response(PR),37 cases(58.7%)had stable disease(SD),and 8 cases(12.7%)developed progressive disease(PD).The median PFS were 12.0 months and the median OS were 24.0 months.The frequency and severity of adverse events correlated with tumor response rate(both with P < 0.05).Multivariate analysis showed the independent predictors of better PFS included diarrhea(OR 0.255,95 % CI 0.130-0.500,P=0.000)and rash(OR 0.235,95 % CI 0.114-0.482,P=0.000).For OS,diarrhea(OR 0.454,95%CI 0.246-0.839,P=0.012),rash(OR 0.405,95%CI 0.211-0.776,P=0.006)and hypertension(OR 0.373,95%CI 0.177-0.784,P=0.009)correlated with better OS.2.Among 104 patients,10 patients(19.2%)caused recurrence of tumors in the sorafenib group and 6 patients(11.5%)did in the control group.The median DFS was 23.5months in the sorafenib group and 19.5 months in the control group.There was no significant difference in tumor recurrence rate between the two groups(HR 0.721,95% CI0.262-1.987,P = 0.525).Logistics regression analysis showed that TNM stage,Fuhrman grade,UISS grade,and postoperative creatinine increase were related recurrence factors.Multivariate analysis showed that Fuhrman grade ≥3 is an independent risk factor for tumor recurrence(HR 25.364,95% CI 2.874-223.810,P = 0.004).Conclusion: 1.The efficacy of sorafenib in the treatment of mRCC patients is positively correlated with the frequency and severity of adverse events.Diarrhea and rash are independent protective factors of PFS.Diarrhea,rash and hypertension are independent protective factors of OS.More samples of prospective study are still needed to explore.2.We don’t find expected benefits on sorafenib used in adjuvant treatment of renal cell carcinoma.Further research is needed to evaluate its value in the adjuvant treatment of renal cell carcinoma.TNM staging,Fuhrman classification,UISS classification,and postoperative creatinine elevation are related factors of recurrence.Multivariate analysis showed that Fuhrman classification ≥3 is an independent risk factor of recurrence.