Correlation analysis between sunitinib-induced hypertension and efficacy in patients with metastatic renal cell carcinoma
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摘要: 目的:探讨分析高血压不良反应与舒尼替尼治疗晚期转移性肾癌疗效的相关性。方法:回顾性收集我院2009年1月~2016年6月65例舒尼替尼治疗的晚期转移性肾癌患者的临床资料,男42例,女23例;年龄44~75岁,平均63岁;84.6%的患者接受手术治疗(肾癌根治性切除或保留肾单位切除),肿瘤病理均为肾透明细胞癌,最常见的转移部位为肺(73.8%)。所有患者均采用舒尼替尼标准治疗方案:50 mg/d,服用4周,停用2周。每2个周期通过CT检查评价药物疗效,每个疗程的第1天和第28天检测血压。比较有无舒尼替尼诱导的高血压不良反应[收缩压≥140 mmHg(1 mmHg=0.133 kPa)或者舒张压≥90 mmHg]对肿瘤疗效的影响。结果:服用靶向药物期间,根据是否出现高血压不良反应进行分组,分为高血压组(30例)和血压正常组(35例),两组基线特征比较差异均无统计学意义。高血压不良反应在舒尼替尼治疗的第1疗程或者第2疗程出现,出现收缩期的高血压(中位时间:第1疗程,1~9疗程)比舒张期的高血压(中位时间:第2疗程,1~11疗程)更为早期。在12个月的随访中,高血压组客观有效率(ORR)显著高于血压正常组(56.7%vs.28.6%,P=0.016)。同时亚组分析收缩期高血压组或舒张期高血压组与收缩压正常组或舒张压正常组比较差异均有统计学意义(P=0.039、P=0.038)。长期随访过程中,高血压组平均无进展生存期(PFS)较血压正常组显著延长(13.4个月vs.8.7个月,P=0.002)。结论:在舒尼替尼治疗过程中,晚期转移性肾癌患者出现高血压不良反应可获得更好的肿瘤控制,更长的PFS,适合作为预测靶向药物疗效的有效指标。Abstract: Objective: To investigate the relationship between sunitinib-induced hypertension and efficacy in patients with metastatic renal cell carcinoma. Method: The clinical data of 65 patients with metastatic renal cell carcinoma treated with sunitinib were collected retrospectively from January 2009 to June 2016. There were 42 males and 23 females, with an average age of 63(range, 44-75) years old. There were 84.6% patients who underwent surgery(radical nephrectomy or partial nephrectomy). The tumor pathology was clear cell renal cell carcinoma. The most common metastatic site was lung(73.8%). All patients received the standard dosing schedule of sunitinib: 50 mg daily for 4 weeks on and 2 week off. The efficacy was assessed by CT examination every 2 cycles and blood pressure was measured on days 1 and 28 of each cycle of treatment. Moreover, we evaluated the relationship between sunitinib-induced hypertension(systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) and the efficacy of the treatment. Result: Patients were divided into hypertension group(n=30) and normal blood pressure group(n=35) according to adverse events of hypertension during patients treated with sunitinib. There was no significant difference in baseline characteristics between the two groups. Sunitinib-induced hypertension often occurred during the first or second cycle of treatment. The increasing of systolic blood pressure(median time: cycle 1, range: 1 to 9 cycle) occurred earlier, compared with the increasing of diastolic blood pressure(median time: cycle 2, range: 1 to 11 cycle). During follow-up period of 12 months, the objective response rate was significantly higher in the hypertension group(17 patients, 56.7%) than that in the normal blood pressure group(10 patients, 28.6%)(P=0.016). Through subgroup analysis, there was significant statistical difference between systolic hypertension group or diastolic hypertension group and normal blood pressure group(P=0.039, P=0.038). During long-term follow-up, the mean progression-free survival time(13.4 months, 95%CI: 11.2-15.6) in the hypertension group was significantly longer than that in the normal blood pressure group(8.7 months, 95%CI: 7.0-10.5)(P=0.002).Conclusion: Patients with sunitinib-induced hypertension achieve better tumor control and longer progression-free survival, which is suitable for predicting the efficacy of treatment.
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