舒尼替尼治疗转移性肾细胞癌的疗效和不良反应及其相关性分析

Efficacy and safety of sunitinib in treating metastatic renal cell carcinoma

目的 评价舒尼替尼治疗转移性肾细胞癌的疗效及安全性,并分析疗效与不良反应的相关性. 方法 2008年6月至2013年3月91例转移性肾细胞癌患者接受舒尼替尼治疗.其中男73例,女18例.年龄17～77岁,中位年龄58岁.行根治性肾切除术83例,肾穿刺活检或转移灶穿刺活检8例.肾透明细胞癌86例,肾乳头状细胞癌4例,未分类肾癌1例.一线治疗77例,细胞因子治疗失败者8例,索拉非尼治疗进展后二线治疗6例.81例口服舒尼替尼50 mg/d 4周,停药2周,6周为1个周期;10例口服舒尼替尼37.5 mg/d,持续用药.治疗期间根据不良反应的严重程度调整用药,直至出现疾病进展或出现不可耐受的不良反应. 结果 中位随访时间19.0个月.完全缓解2例（2.2％）,部分缓解23例（25.3％）,疾病稳定57例（62.6％）,疾病进展9例（9.9％）.客观缓解率为27.5％,疾病控制率为90.1％.获得疾病控制患者达到最佳疗效的中位时间为5.5个月（2.0～27.0个月）.中位无疾病进展时间15.5个月.主要不良反应包括血小板减少71例（78.0％）,甲状腺功能异常43例（76.8％,43/56）,手足皮肤反应68例（74.7％）,白细胞减少57例（62.6％）,高血压44例（48.4％）,乏力43例（47.3％）.3～4级不良反应38例,主要包括血小板减少14例、中性粒细胞减少8例、手足皮肤反应7例及甲状腺功能异常6例.31例（34.1％）患者因不良反应需要调整药物剂量或短暂停药,多数患者经对症支持后可继续治疗,2例患者分别因严重乏力和心肌梗死中断治疗.出现1～2级不良反应与出现3～4级不良反应患者的中位无疾病进展生存期分别为11.5个月和18.0个月（p=0.04）. 结论 舒尼替尼用于治疗转移性肾细胞癌患者具有较好的疗效和安全性,可获得较长的无进展生存期.多数不良反应可以耐受,出现3～4级不良反应可能是治疗有效的预测因子.

Objective To evaluate the efficacy,safety and their correlation of sunitinib in the treatment of metastatic renal cell carcinoma （mRCC）.Methods Ninety-one cases with mRCC were treated with sunitinib between June 2008 and March 2013,including 73 males and 18 females.The median age was 58 （17-77） years.All patients were diagnosed as RCC,which consisted of 86 clear cell carcinomas,4 papillary cell carcinomas and 1 unclassified RCC.Seventy-seven cases were treated with first line therapy and 14 cases showed progression on first-line cytokine or sorafinib therapy.Daily oral sunitinib monotherapy was administered for 4 weeks,followed by 2 weeks off by repeated 6-week cycles in 81 patients,while another 10 patients received 37.5 mg Qd continuously until disease progression or unacceptable toxicities occurred.Results The median follow-up was 19.0 months.Two （2.2%） patients achieved complete responses,23 （25.3%） patients achieved partial responses,57 （62.6%） patients demonstrated stable disease for ≥ 3 months and 9 （9.9%） patients developed progressive disease.The objective response rate was 27.5%,and the disease control rate was 90.1%.The median progression-free survival （PFS） was 15.5 months.The most common treatment-related adverse events were thrombocytopenia （71 cases,78.0%）,thyroid dysfunction （43/56,76.8%）,hand-foot syndrome（68 cases,74.7%）,leucopenia （57 cases,62.6%）,hypertension （44 cases,48.4%）,fatigue （43 cases,47.3%）.The grade 3-4 major adverse events （38 cases） included thrombocytopenia （14 cases）,neutropenia（8 cases）,hand-foot syndrome （7 cases） and thyroid dysfunction （6 cases）.Thirty-one （34.1%） patients had dose decrement or drug discontinuation.Two patients withdrew fiom treatment for intolerable fatigue and cardiac infarction.The median PFS was significantly improved in patients with grade 3-4 adverse events compared with those with only grade 1-2 adverse events（18.0 versus 11.5 months,P=0.04）.Conclusions The efficacy of sunitinib in patients with mRCC is encouraging.At the same time,the tolerability is good.Sunitinib-associated severe adverse events may be a predictive marker for treatment efficacy in mRCC.