舒尼替尼治疗晚期肾细胞癌的疗效和安全性

摘要

Background and purpose:The effectiveness of sunitinib in the treatment of metastatic renal cell carcinoma has been verified by phaseⅡandⅢclinical trails. Sunitinib is approved multinationally for the first-line treatment of advanced renal cell carcinoma. Our study was designed to evaluate the safety and efficacy of sunitinib in the treatment of advanced renal cell carcinoma. Methods:A total number of 52 patients with advanced renal cell carcinoma were enrolled from Aug. 2008 to Dec. 2011, during which, 43 were male, 9 were female, the median age was 54.5 years (ranged from 29 to 76 years). Forty-five patients received prior radical nephrectomy, 7 patients received biopsy. Forty-eight patients were diagnosed as renal clear cell carcinoma, 4 patients were diagnosed as renal papillary cell carcinoma. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral 50 mg for 4 weeks, followed by 2 weeks off. CT or MRI scan was used to evaluate the efficacy every 2 cycles. Results:Follow ups were raging from 1 to 36 months. Forty-nine patients could be evaluated the efficacy, 3 patients discontinued for lacking of financial support. The disease control rate was 87.8%, 2 (4.1%) patients with complete response (CR), 10 (20.4%) patients with partial response (PR), 31 (63.3%) patients with stable disease (SD), and 6 (12.2%) patients with progression disease (PD) as the best tumor response. The 1-year control rate was 61%, and the 1-year survival rate was 85%. Median progression-free survival (PFS) was 15 months, and median overall survival (OS) was 23 months. According to the pathological types, metastatic sites, and ECOG status, the patients were divided into subgroups. In patients with clear cell renal cell carcinoma, median PFS was 12 months, and median OS was 23 months. Median PFS was longer in patients with single-organ metastasis compared with multi-organ metastases subgroup (18 vs 9 month), surgery compared with biopsy subgroup (18 vs 8 month), and ECOG 0 score compared with ECOG 1 score subgroup (15 vs 12 month). Median OS has not been reached in single-organ metastasis compared with 12 months in multi-organ metastasis subgroup, was 23 months in surgery compared with 9 months in biopsy subgroup, and has not been reached in ECOG 0 score compared with 23 months in ECOG 1 score subgroup. The most common adverse events were hand-foot syndrome, fatigue, leucopenia, thrombocytopenia, mucositis, and hypertension. Grade 3 adverse events included hand-foot syndrome, leucopenia, thrombocytopenia, anemia, diarrhea, mucositis, hypothyroidism, vomiting, and facial edema. All adverse events were ameliorated by supportive treatment or dose reduction. Conclusion:Sunitinib was efficacious in the treatment of advanced renal cell carcinoma. Most adverse events were tolerable, and grade 3 adverse events need medical treatment.%　　背景与目的：舒尼替尼治疗转移性肾癌的有效性已经被Ⅱ期和Ⅲ期临床实验验证,在多个临床指南中推荐为晚期肾癌的一线治疗方案.本研究观察舒尼替尼治疗晚期肾细胞癌的疗效和安全性.方法：中国医学科学院肿瘤医院于2008年8月—2011年12月收治晚期肾细胞癌患者52例,男性43例,女性9例.年龄29~76岁,中位年龄54.5岁.原发肾脏病灶手术切除45例,穿刺病理证实7例.肾透明细胞癌48例,肾乳头状细胞癌4例.治疗方案：舒尼替尼50 mg,每天1次,治疗4周停2周为1个周期；每2个周期行影像学检查评价疗效.结果：随访1~36个月,3例因患者经济情况停药,49例可评价疗效.完全缓解(complete remission,CR)2例(4.1%),部分缓解(partial remission,PR)10例(20.4%),疾病稳定(stable disease,SD)31例(63.3%),疾病进展(progression of disease,PD)6例(12.2%),疾病控制率(CR+PR+SD)为87.8%.1年疾病控制率为61%,1年生存率为85%.中位疾病无进展期(progression free survival,PFS)为15个月,中位总生存时间(overall survival,OS)为23个月.根据病理类型、转移部位和体力状况评分等将患者分为亚组进一步统计.肾透明细胞癌组中位PFS为12个月,中位OS为23个月.中位PFS在单脏器转移组为18个月,多脏器转移组为9个月,在术后病理确诊组为18个月,在穿刺病理确诊组为8个月；在美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)评分分组中,0分组为15个月,1分组为12个月.中位生存时间在单脏器转移组未达到,多脏器转移组为12个月；在术后病理确诊组为23个月,在穿刺病理确诊组为9个月；在ECOG为0分组未达到,在ECOG为1分组为23个月.常见不良反应包括手足皮肤反应、乏力、白细胞降低、血小板降低、口腔黏膜炎及高血压等,发生的Ⅲ级不良反应包括手足皮肤反应、白细胞降低、血小板降低、贫血、腹泻、口腔黏膜炎、甲状腺功能减低、呕吐和浮肿.通过对症支持及减量,不良反应可以控制并耐受.结论：舒尼替尼治疗晚期肾细胞癌疗效显著,常见不良反应患者可耐受,严重不良反应需要医疗干预.