索拉非尼治疗转移性肾癌疗效与不良反应的关系

The relationship between the efficacy and adverse events of sorafenib in the treatment of metastatic renal cell carcinoma

目的:探索索拉非尼在治疗转移性肾细胞癌(mRCC)患者中的不良反应与疗效之间的关系。方法:回顾性研究西京医院接受索拉非尼治疗的mRCC患者63例,利用卡方检验分析肿瘤控制率与不良反应的发生频率和严重程度的相关性,利用Kaplan-Meier方法分析16种不良反应,筛选出与患者PFS,OS相关的不良反应,将P<0.05变量纳入多变量Cox比例风险回归模型进行进一步的多因素分析,确定独立预后因素。结果:63例接受索拉非尼治疗的患者中,完全缓解2例(3.2%),部分缓解16例(25.4%),疾病稳定37例(58.7%),疾病进展8例(12.7%)。中位PFS为12.0个月,中位OS为24.0个月。卡方检验结果示肿瘤控制率与不良反应的发生频率和严重程度相关(均P<0.05)。多变量分析显示,更好的PFS的独立预后因素包括腹泻(OR 0.255,95%CI 0.130~0.500,P=0.000)和皮疹(OR 0.235,95%CI 0.114~0.482,P=0.000)。OS的独立预后因素包括腹泻(OR 0.454,95%CI 0.246~0.839,P=0.012),皮疹(OR 0.405,95%CI 0.211~0.776,P=0.006)和高血压(OR 0.373,95%CI 0.177~0.784,P=0.009)。结论:索拉非尼治疗mRCC患者的疗效与不良反应的发生频率和严重程度呈正相关。皮疹和腹泻是影响PFS的独立保护因素,皮疹,腹泻和高血压是影响OS的独立保护因素。这一结论仍需大量前瞻性研究证实。

Objective:To explore the relationship between the adverse events and efficacy of sorafenib in patients with metastatic renal cell carcinoma(mRCC).Methods:A retrospective study of 63 patients with mRCC treated by sorafenib in Xijing Hospital was implemented.The correlation between the tumor response rate and the frequency and severity of the adverse events was analysed by Chi-square test.The Kaplan-Meier method was used to analyze the adverse events.The adverse events related to 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.Results: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 was 12.0 months and the median OS was 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)were correlated with better OS.Conclusion: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.