索拉非尼治疗25例晚期肾癌的长期不良反应研究

Long-term adverse reaction of sorafenib in the treatment of advanced renal cell carcinoma in 25 cases

摘要:

目的：了解索拉非尼治疗晚期肾细胞癌（renal cell carcinoma，RCC）患者长期不良反应，评估其对患者预后的预测作用。方法：25例晚期RCC患者口服索拉非尼，观察其不良反应的发生、分级及转归，并采用Kaplan-Meier单因素分析其对患者预后预测作用。结果：25例晚期RCC患者随访6~59月，中位随访时间23.8月。不良反应出现在1～8周，中位不良反应发生时间3周。常见不良反应发生率：高血压48%、贫血36%、疲乏44%、腹泻40%、皮疹40%、手足综合征56%，体质量减轻、恶心、厌食、疼痛、脱发等不良反应少见，多为Ⅰ、Ⅱ级。76%患者对症处理后，部分不良反应症状减轻或消失，中位时间20周，20%患者反应较轻，4%患者反应较重，药物减量后不良反应减轻。高血压的患者较未发生高血压的患者中位总生存期（overall survival，OS）及无进展生存时间（progression-free survival，PFS）明显缩短（OS：P=0.005；PFS：P=0.049）。结论：索拉非尼治疗RCC不良反应发生较早，长期使用大部分不良反应可以耐受，高血压对患者生存期有预测作用。

Abstract:

Objective：To investigate the long-term adverse effects of sorafenib on patients suffering from renal cell carcinoma（RCC） and to evaluate its predictive effects on survival time of patients with RCC. Methods：The occurrence，grading and prognosis of adverse effects of 25 advanced RCC patients treated by sorafenib were recorded and their predictive effects on survival time of patients were evaluated by Kaplan-Meier estimator. Results：According to 6-59 months’ follow-up；median follow-up of 23.8 months with 25 advanced RCC patients，the adverse effects appeared in 1-8 weeks；medium follow-up of 3 weeks. The common adverse reactions were hypertension（48%），anemia（36%），fatigue（44%），diarrhea（40%），skin rash（40%），and PPE（56%）. The relatively rare adverse reactions were mostly between level Ⅰ and level Ⅱ，including weight loss，nausea，anorexia，pain，and hair loss，etc. After the symp－tomatic treatment，the symptoms of 76% patients were partly relieved or disappeared，median relieving period of 20 weeks，20% pa－tients got relatively mild adverse reaction while 4% patients got relatively severe adverse reaction. The adverse effects were relieved after reducing medicine dose. The overall survival and progression-free survival of patients with hypertension were significantly shorter than those without hypertension（P=0.005；PFS：P=0.049）. Conclusion：The adverse effect appears at early period of patients with advanced RCC when taking sorafenib and most adverse effects are acceptable in long-term medicating for patients. Hypertension might have a predictive effect on survival period of patients.