影响安罗替尼临床疗效和预后的多因素分析

目的:观察经过安罗替尼治疗的不同瘤种恶性肿瘤患者的相关指标，探索影响安罗替尼临床疗效和预后的因素。方法:2018年7月至2019年12月使用安罗替尼治疗的晚期恶性肿瘤患者101例，取患者治疗过程中的血液，用ELISA法和实时荧光定量PCR法检测血清中VEGF、FGF、c-Kit、Bcl-2、PARP蛋白含量和mRNA相对表达量。另一方面，评价安罗替尼的疗效和随访观察PFS。结果:全部病例的总的中位PFS为4.8月（95%CI:3.8~5.8），PR 18例（17.82%），SD 61例（60.40%），PD 22例(21.78%)，ORR 17.82%，DCR 78.22%。TSH升高患者的DCR较未发生者高（P=0.039 0）。既往曾使用铂类化疗者较未使用者具有更长的中位PFS（5.3月 vs 3.6月,Log-rank P=0.038 0），TSH升高患者较未升高患者的中位PFS显著延长（6.4月 vs 4.0月，Log-rank P=0.046 0），发生手足综合征者中位PFS较未发生者显著延长（11.4月 vs 4.2月，Log-rank P=0.021 0）。血清bFGF的蛋白含量（P=0.009 0）及Bcl-2 mRNA相对表达量（P=0.012 0）是安罗替尼治疗晚期恶性肿瘤预后的独立影响因子。结论:血清bFGF含量及Bcl-2 mRNA表达量是安罗替尼疗效的独立影响因素；既往曾使用铂类、发生手足综合征和促甲状腺素升高者具有更长的PFS。

Multi-factor analysis on the clinical efficacy and the prognosis of anlotinib

Objective:To observe the relative indexes of patients with different types of malignant tumors treated with anlotinib and to explore the factors affecting the clinical efficacy and prognosis of anlotinib.Methods:From July,2018 to December,2019,101 patients with advanced malignant tumors were treated with anlotinib.The blood of the patients during the treatment was collected,and the serum levels of VEGF,FGF,c-Kit,Bcl-2,PARP and relative mRNA expression were detected by ELISA and real-time quantitative PCR.On the other hand,the efficacy of anlotinib were evaluated,and PFS was observed.Results:The median total PFS was 4.8 months(95%CI:3.8~5.8).There were 18 cases of PR(17.82%),61 cases of SD(60.40%),22 cases of PD(21.78%).ORR was 17.82%,and DCR was 78.22%.Patients with elevated TSH had higher DCR than those without elevated TSH(P=0.039 0).Patients with previous platinum chemotherapy had a longer median PFS(5.3 months vs 3.6 months,Log-rank P=0.038 0).The median PFS of patients with elevated TSH was significantly longer than that of patients without elevated TSH(6.4 months vs 4.0 months,Log-rank P=0.046 0),and the median PFS of patients with hand-foot syndrome was significantly longer than that of patients without elevated TSH(11.4 months vs 4.2 months，Log-rank P=0.021 0).The protein content of serum bFGF(P=0.009 0)and the relative expression of Bcl-2 mRNA(P=0.012 0)were independent influencing factors for the prognosis of advanced malignant tumors treated with anlotinib.Conclusion:The content of serum bFGF and the expression of Bcl-2 mRNA were independent factors influencing the efficacy of anlotinib.Patients with previous use of platinum,hand-foot syndrome and elevated thyrotropin had longer PFS.