舒尼替尼治疗转移性肾癌的疗效和安全性分析:单中心37例总结

目的 评价舒尼替尼治疗转移性肾细胞癌的疗效和安全性.方法 2008年6月至2010年4月37例转移性肾细胞癌患者接受舒尼替尼治疗.其中男28例,女9例.年龄17～74岁,中位年龄52岁.行根治性肾切除手术33例,肾穿刺活检3例,腋窝转移淋巴结穿刺活检1例.vonHippel-Lindau综合征患者2例.肾透明细胞癌36例,其中伴颗粒细胞成分1例、伴肉瘤样分化4例,肾乳头状细胞癌1例.一线治疗30例,细胞因子或索拉非尼治疗进展后二线治疗7例.其中34例采用4/2方案,即口服舒尼替尼50.0 mg/d 4周,停用2周,6周为1个周期;3例予口服37.5 mg/d持续治疗,直至疾病进展或者出现不可耐受的不良反应.结果 中位随访时间12个月(8个周期).34例患者治疗2周期以上,可进行疗效评估.根据RECIST标准评价最佳疗效,部分缓解9例(26.5%),疾病稳定24例(70.6%),疾病进展1例(2.9%).客观反应率26.5%,疾病控制率97.1%.1年生存率95.8%(23/24),1年无进展生存率62.5%(15/24).主要不良反应包括血小板减少30例(81.1%)、甲状腺功能异常18/22例(81.8%)、手足反应27例(73.0%),白细胞减少23例(62.2%)、高血压18例(48.6%)等.大多数不良反应为1～2级,3级以上不良反应包括血小板降低8例(21.6%)、甲状腺功能异常4/22例(18.2%)、手足反应4例(10.8%)、血磷降低4例(10.8%)和腹泻2例(5.4%)等.10例(27.0%)在治疗过程中减量或停药,1例因严重乏力不能耐受终止治疗.通过对症支持,减量或停药,不良反应可控制并耐受.结论 舒尼替尼一线及二线治疗晚期转移性肾细胞癌可取得较高的疾病控制率,不良反应发生率多数轻而易耐受,严重不良反应较少且可控.

Abstract：

Objective To evaluate the efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma (RCC). Methods A total of 37 patients with metastatic RCC were treated with between June 2008 and April 2010, including 28 males and 9 females. The median age was 52 (17-74) years. All patients received a pathologic diagnosis of RCC, which consisted of 1 papillary cell carcinoma and 36 clear cell carcinomas, 4 of which accompanied with partial sarcoma differentiation. Thirty cases were treated with first line therapy and 7 cases showed progression on first-line cytokine or sorafinib therapy. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients, while another 3 patients received 37. 5 mg Qd continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. Results The median follow up was 12 months (8 cycles),range 1.5-19. 5 months (1-13 cycles). 26.5% (9/34) patients achieved partial responses, 70.6%(24/34) patients demonstrated stable disease over≥3 months and 1 (2. 9%) patient developed progressive disease. The objective response rate was 26.5%, and the disease control rate was 97. 1%.The 12 months' overall survival rate was 95.8% (23/24), and 12 months' progression-free survival rate was 62.5 % (15/24). The most common treatment-related adverse events were thrombocytopenia (30 cases, 81.1%), thyroid dysfunction (18/22, 81.8%) ,hand-foot syndrome (27 cases, 73.0%),neutropenia (23 cases, 62.2%) and hypertension (18 cases, 48.6%). The major grade 3 adverse events included thrombocytopenia (8 cases, 21.6%), hand-foot syndrome (4 cases, 10.8%) and diarrhea (2 cases, 5. 4%). Most adverse events were ameliorated by treatment interruption. Ten (27.0%) patients had dose decrement or drug discontinuation and 1 patient quit the treatment for intolerable fatigue. Conclusion The efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic RCC.     

舒尼替尼治疗转移性肾癌的疗效和安全性分析:单中心37例总结

Objective To evaluate the efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma (RCC). Methods A total of 37 patients with metastatic RCC were treated with between June 2008 and April 2010, including 28 males and 9 females. The median age was 52 (17-74) years. All patients received a pathologic diagnosis of RCC, which consisted of 1 papillary cell carcinoma and 36 clear cell carcinomas, 4 of which accompanied with partial sarcoma differentiation. Thirty cases were treated with first line therapy and 7 cases showed progression on first-line cytokine or sorafinib therapy. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients, while another 3 patients received 37. 5 mg Qd continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. Results The median follow up was 12 months (8 cycles),range 1.5-19. 5 months (1-13 cycles). 26.5% (9/34) patients achieved partial responses, 70.6%(24/34) patients demonstrated stable disease over≥3 months and 1 (2. 9%) patient developed progressive disease. The objective response rate was 26.5%, and the disease control rate was 97. 1%.The 12 months' overall survival rate was 95.8% (23/24), and 12 months' progression-free survival rate was 62.5 % (15/24). The most common treatment-related adverse events were thrombocytopenia (30 cases, 81.1%), thyroid dysfunction (18/22, 81.8%) ,hand-foot syndrome (27 cases, 73.0%),neutropenia (23 cases, 62.2%) and hypertension (18 cases, 48.6%). The major grade 3 adverse events included thrombocytopenia (8 cases, 21.6%), hand-foot syndrome (4 cases, 10.8%) and diarrhea (2 cases, 5. 4%). Most adverse events were ameliorated by treatment interruption. Ten (27.0%) patients had dose decrement or drug discontinuation and 1 patient quit the treatment for intolerable fatigue. Conclusion The efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic RCC.     

舒尼替尼治疗转移性肾癌的疗效及安全性评价

目的 评价舒尼替尼治疗转移性肾癌的疗效及安全性. 方法转移性肾癌患者15例.男10例,女5例.中位年龄56(37～73)岁.曾行原发肿瘤切除术13例,行CT引导下肿瘤穿刺活检术2例.组织学类型为透明细胞癌14例,乳头状细胞癌1例.舒尼替尼50 mg/d连续给药4周,停药2周方案4例;37.5 mg/d持续口服方案11例.评价肿瘤治疗疗效、患者无疾病进展生存时间及总体生存时间,同时观察治疗相关不良反应. 结果中位随访时间13(2～24)个月,15例均可评价疗效,其中部分缓解8例、疾病稳定5例、疾病进展2例.总客观缓解率53%(8/15),疾病控制率87%(13/15).由于随访时间短,尚不能报告中位无进展生存时间和总生存时间.常见不良反应包括手足皮肤反应11例(73%),头发颜色改变10例(67%),口腔溃疡、脱发各9例(60%),腹泻、中性粒细胞减少各8例(53%).多数不良反应为1～2级,且所有不良反应均可逆. 结论舒尼替尼治疗晚期转移性肾癌疗效显著,具有较高的肿瘤客观缓解率,大多数不良反应较轻且可逆,患者多可耐受,安全性较好,但长期疗效及安全性需进一步随访.     

舒尼替尼治疗转移性肾癌的初步评价

目的 评价舒尼替尼治疗转移性肾癌的疗效和安全性. 方法转移性肾癌患者31例.男23例,女8例.中位年龄55(25～75)岁.31例中行原发肿瘤切除30例,仅行活检术1例,病理证实为肾细胞癌,并至少有1处可测量的转移病灶.初始患者均口服舒尼替尼50 mg/d,用药4周、间歇2周为1个周期,每2个周期行CT扫描以评价疗效. 结果全组可评价疗效24例,无完全缓解病例,部分缓解5例、疾病稳定15例、疾病进展4例,其中死亡1例.中断治疗4例,其中因高龄、全身情况差、不能耐受服药1例,因经济困难停药2例,因肝功能损害停药1例.3例因治疗时间短而未评价.全组客观反应率21%(5/24),疾病控制率83%(20/24),中位无疾病进展生存时间11个月,1年无进展生存率80%.常见不良反应是手足皮肤反应、腹泻、食欲差、口腔炎、出血倾向和血液学毒性,分别通过外敷、口服药物和补液治疗得到及制. 结论舒尼替尼对转移性肾癌的病情控制有显著效果,也存在一定不良反应,通过及时干预和处理,患者大多可以耐受其不良反应.     

舒尼替尼治疗转移性非透明细胞肾癌的疗效观察

目的 初步探讨舒尼替尼治疗转移性非透明细胞肾癌的疗效.方法 非透明细胞肾癌22例.男14例,女8例.年龄29～76岁,中位年龄46岁.根治性肾切除术后出现转移14例,初诊时诊断为肾癌伴转移行减瘤性肾切除术8例.病理证实乳头状癌12例,嫌色细胞癌1例,集合管癌3例,未分类癌6例.转移部位包括肺、淋巴结、肾上腺,骨和肝脏.舒尼替尼50mg/d,口服,每天1次,治疗4周休息2周.治疗时间4.5 ～24.0个月,中位时间11个月.随访4.5 ～25.0个月,中位时间14个月.结果 22例疾病控制率为73％ (16/22).部分缓解4例(18％),其中乳头状癌3例,嫌色细胞癌1例,转移灶位于肺或肺加腹膜后淋巴结,或腹膜后淋巴结.疾病稳定＞3个月12例(55％),用药3个疗程内疾病进展6例(27％).结论 舒尼替尼治疗转移性肾乳头状癌、嫌色细胞癌、集合管癌、未分类癌有效,对淋巴结转移及肺转移者的疗效相对较好.     

舒尼替尼治疗转移性肾癌的近期疗效及耐受性

目的 探讨舒尼替尼治疗转移性肾癌两种方案的疗效、不良反应特点及其相应处理方法.方法 舒尼替尼治疗晚期转移性肾癌病例45例,男25例,女20例,年龄36～78岁,平均48岁.随机分为2组,第1组:25例,舒尼替尼50 mg/d口服,用药4周、间歇2周为1个周期.第2组:20例,舒尼替尼口服,37.5 mg/d,连续服用.观察评估治疗中出现的不良反应及相应的处理方法.结果 全组可评估疗效40例,完全缓解1例,部分缓解3例,稳定28例,进展8例(死亡4例).全组疾病控制率为80%(32/40).2级以上的不良反应发生率:2组高血压分别有32%(8/25)与10%(2/20),P=0.02;肝功能损害分别为32%(8/25)与20%(4/20),P=0.011;手足皮肤反应分别为68%(17/25)与60%(12/20),血液学毒性分别为68%(17/25)与50%(10/20),口腔黏膜、反流性食管炎及胃炎分别为56%(14/25)与50%(10/20),疲劳乏力分别为64%(16/25)与40%(8/20).不良反应出现时间不同,但大多在服药3个月内出现.结论 舒尼替尼治疗转移性肾癌所产生的绝大多数常见不良反应发生率与国外报道略有不同,但通过严格随访,积极预防及对症处理,服药后安全性良好.舒尼替尼37.5 mg/d,连续服用在肝功能损伤、高血压等方面优于间歇服用的方案.

Abstract：

Objective To evaluate the clinical efficacy and side effects of sunitinib in the treatment of advanced renal cell carcinoma. Methods Forty-five patients with advanced renal cell carcinoma and an average age of 48.6 yrs were treated with sunitinib. Among the study group, 25 were male and 20 were female. In group one, patients received sunitinib treatment in repeated six week cycles consisting of four weeks of sunitinib 50 mg daily followed by two weeks off treatment (schedule 4/2). In group two, a single daily dose of sunitinib 37.5 mg was administrated to 20 patients without off treatment. A CT scan was used to evaluate the treatment efficacy after each cycle and the side effects were recorded accordingly. Results Clinical efficacy could be evaluated in 40 patients. Of these, two achieved complete response, eight achieved partial response, 27 were stable and the remaining eight experienced disease progression with four patients dying during the study period. The side effects of sunitinib in group one and in group two included hypertension 32% (8/25) and 10% (2/20), P=0.02; liver function impairment 32% (8/25) and 20% (4/20), P=0.011; hand-foot skin reaction 68% (17/25) and 60% (12/20), respectively. The incidence of major side effects of sunitinib were different in Chinese patients than from what had been previously reported in studies conducted in US and Europe. Generally, most of the sunitinib side effects were easy to manage. Conclusions There weredifferences between the two groups of Chinese patients treated with different sunitinib protocols. The protocol of sunitinib 37.5mg daily without off-treatment was better than the protocol of sunitinib 50mg daily (schedule 4/2) in regard to liver function impairment and hypertension.     

舒尼替尼一线治疗转移性肾癌初探

目的 观察舒尼替尼一线治疗转移性肾癌的疗效及安全性.方法 对经病理确诊的46例转移性肾透明细胞癌患者给予舒尼替尼治疗,50 mg,每天1次,服用4周,休息2周,6周为1个周期.2个周期评价疗效,有效或病情稳定者继续口服舒尼替尼治疗.结果 46例患者中病情部分缓解(PR)15例(32.6%),病情稳定(SD)25例(54.3%),疾病进展(PD)6例(13.1%);全组有效率32.6%(95%CI:19.1%～46.1%),疾病控制率86.9%,中位无进展生存期11个月,1年生存率65.2%,中位总生存期尚未达到.主要不良反应:疲乏33例(71.7%)、皮肤黄染29例(63.0%)、食欲减退28例(60.9%)、手足皮肤反应26例(56.5%)、口腔黏膜炎25例(54.3%)、高血压19例(41.3%)、颜面水肿18例(39.1%)、腹泻17例(37.0%)、出血17例(37.0%)、恶心15例(32.6%)等;血液学毒性方面:白细胞减少32例(69.6%)、中性粒细胞减少30例(65.2%)、血小板减少28例(60.9%)、贫血21例(45.7%),3～4级严重不良反应主要为血小板减少[15例(32.6%)].结论 舒尼替尼一线治疗转移性肾癌疗效显著,不良反应多为轻中度,3～4级血小板减少应引起重视.

Abstract：

Objective To evaluate the efficacy and safety of sunitinib as first line treatment in patients with metastatic renal cell carcinoma (RCC). Methods This study included 46 Chinese patients who were diagnosed with metastatic RCC after radical nephrectomy. The patients received oral sunitinib (50 mg once daily on a 4 weeks on, 2 weeks off) on a 6 weeks cycle dose schedule until disease progression or intolerable toxicities occurred. Results The overall objective response rate was 32.6% (95% confidence interval [CI, 19.1% to 46. 1%]), and the disease control rate was 86.9%,with complete response (CR) 0 (0%), partial responses (PRs) 15 (32.6%), stable disease (SD) 25(54.3 %), and progression disease (PD) 6 ( 13. 1%). The median progression-free survival was 11 months, and the 1-year survival rate was 65.2%, while the median overall survival (mOS) has not been reached. The main adverse events included fatigue 33 (71.7%), skin discoloration 29 (63.0 %),anorexia 28 (60.9%), hand-foot syndrome 26 (56.5%), oral mucositis 25 (54.3%), hypertension 19 (41.3%), facial edema 18 (39.1%), diarrhea 17 (37.0%), hemorrhage 17 (37.0%), nausea 15 (32.6%), and hematological toxicity: leukopenia 32 (69.6%), neutropenia 30 (65.2%), thrombocytopenia 28 (60.9%), anemia 21 (45.7%). Most of grade 3/4 serious adverse events were thrombocytopenia in 15 (32. 6%) patients. Conclusions Sunitinib has a prominent effect in metastatic renal cell cancer in a Chinese population with mostly mild to moderate adverse reactions. More attention should be paid to grade 3/4 adverse reaction of thrombocytopenia.     

舒尼替尼治疗转移性肾脏透明细胞癌的临床研究

目的 评价舒尼替尼治疗转移性肾脏透明细胞癌的疗效和安全性.方法 2008年6月至2009年6月共有23例转移性肾透明细胞癌患者接受舒尼替尼治疗,男性16例,女性7例,中位年龄52岁.其中一线治疗20例,索拉非尼治疗进展后二线治疗3例.患者病理检查均为肾脏透明细胞癌.治疗方案:舒尼替尼50 mg,每天1次,4/2方案,治疗4周停2周为1周期.直至疾病进展或者出现不可耐受的不良反应.结果 中位随访时间7.5个月(5个周期).根据RECIST标准进行疗效评价显示部分缓解(PR)4例(17.4%);疾病稳定(SD)18例(78.3%),疾病进展(PD)1例(4.3%).17例患者治疗超过6个月(4个周期),6个月的生存率为100%,6个月的无进展生存率为88.2%(15/17).不良反应多为Ⅰ～Ⅱ级,Ⅲ级不良反应为手足反应3例(13.0%)、血小板降低2例(8.7%)、腹泻1例(4.3%)和乏力1例(4.3%),Ⅳ级不良反应1例(4.3%).通过对症支持和减量治疗,不良反应大多可以控制并耐受.结论 舒尼替尼一线及二线治疗晚期转移性肾脏透明细胞癌可取得较高的客观控制率,不良反应可控制,严重不良反应少见.     

舒尼替尼治疗晚期肾细胞癌的临床应用

目的 评价舒尼替尼治疗晚期肾细胞癌的疗效和安全性.方法 晚期肾细胞癌患者19例,男16例,女3例,中位年龄54(35～70)岁,随访时间2008年8月至2010年8月.原发肾脏病灶手术切除17例,穿刺病理证实2例.肾透明细胞癌17例,肾乳头状细胞癌2例.治疗方案:舒尼替尼50 mg,每天1次,4/2方案,治疗4周停2周为1个治疗周期;至少每2个周期行影像学检查以确定疗效.结果 随访时间3～22个月,可评价疗效18例,1例因患者经济情况停药.11例患者仍在接受舒尼替尼治疗,1例患者因肿瘤进展停药,6例患者因肿瘤进展死亡.中低危患者14例,中位疾病无进展时间(PFS)18个月,尚未测出中位生存时间.高危患者4例,中位PFS 6个月,中位生存时间8.5个月.根据实体瘤评价标准(RECIST)进行疗效评价,共16例患者服药超过2个周期,2个周期评价部分缓解(PR)2例(12.5%);疾病稳定(SD)14例(87.5%).共10例患者服药超过4个周期,4个周期PR 1例(10.0%); SD 6例(60.0%);疾病进展3例(30.0%).常见不良反应包括手足皮肤反应、口腔溃疡、高血压、味觉改变、乏力、白细胞降低和血小板下降等,发生的Ⅲ级不良反应为手足反应2例(11.1%)、呕吐1例(5.5%)、白细胞降低1例(5.5%)、血小板降低1例(5.5%)、浮肿1例(5.5%).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的控制率较高,大部分不良反应患者可耐受,部分严重不良反应需要医疗干预.     

舒尼替尼治疗转移性肾细胞癌9例报告

目的评价舒尼替尼治疗转移性肾细胞癌的疗效和安全性。方法转移性肾细胞癌患者9例,均为男性。年龄27～79岁（中位年龄56岁）。接受根治性肾切除术者7例,原发灶无法切除者2例。6例曾接受免疫治疗。透明细胞癌8例,乳头状癌1例。转移灶部位：肺转移3例,肝转移4例,淋巴结转移4例,肾上腺转移1例,骨转移1例,脑转移1例,其中4例患者为多发转移。每例患者至少有1处可测量病灶,即目标病灶。治疗时间3～15个月。治疗方案：舒尼替尼50 mg/d,连续服用4周后停药2周,6周为一个周期,直至肿瘤进展或出现不可耐受的不良反应。结果9例均可评价疗效。其中完全缓解1例,部分缓解3例,疾病稳定5例。总缓解率为44.4%（4/9）,疾病控制率为100%（9/9）。中位无进展生存时间42周（16～62周）。常见不良反应有腹泻、乏力、手足综合征、白细胞减少、高血压。结论舒尼替尼治疗转移性肾细胞癌疗效显著,不良反应多为轻中度1～2级。     

索拉非尼治疗转移性非透明细胞肾癌的疗效观察

目的 初步探讨索拉非尼治疗转移性非透明细胞肾癌的疗效.方法 转移性非透明细胞肾癌21例,中位年龄45(25～76)岁.12例为根治性肾切除术后出现转移,9例就诊时诊断为肾癌伴转移,行减瘤性肾切除术.术后病理证实乳头状癌15例、嫌色细胞癌1例、未分类癌5例.转移部位包括肺、淋巴结、肾上腺、骨、肝和甲状腺.治疗方法:①索拉非尼400 mg,2次/d治疗15例;②索拉非尼400 mg,2次/d加干扰素α 300万U,每周连续5 d皮下注射治疗6例.中位治疗时间8(2～21)个月.随访0～22个月.结果 部分缓解(PR)3例(14.3%),其肿瘤病理亚型分别为乳头状癌、嫌色细胞癌和未分类癌各1例,转移灶分别位于腹膜后加纵隔淋巴结、肺加腹膜后淋巴结和腹膜后加盆腔淋巴结.疾病稳定(SD)13例(61.9%),疾病进展(PD)5例(23.8%),疾病控制率76.2%.截至2009年7月,出现PD 13例,中位无疾病进展时间为7(0～21)个月.结论 索拉非尼治疗转移性肾乳头状癌、嫌色细胞癌、未分化癌有效,对淋巴结转移及肺转移者的疗效相对较好.     

索拉非尼治疗具有肉瘤样分化的转移性肾癌的疗效观察

目的 分析索拉非尼治疗具有肉瘤样分化的转移性肾癌的疗效.方法 已行肾脏原发肿瘤切除的转移性肾细胞癌患者14例,病理证实原发肿瘤中含有肉瘤样分化成分.平均年龄61(45～77)岁.肾透明细胞癌伴肉瘤样分化8例,乳头状癌伴肉瘤样分化2例,单纯肉瘤样癌4例,肾原发病灶中肉瘤样成分比例为20%～100%.肿瘤转移部位分别为肺、淋巴结、肾上腺、肝或骨.采用索拉非尼400 mg或600 mg,2次/d治疗.采用Kendall相关检验和Pearson相关检验分别检测肉瘤样成分比例与治疗客观反应及中位无疾病进展时间(PFS)的相关性.中位治疗时间8(3～19)个月.结果 部分缓解(PR)2例,其转移病灶均位于腹膜后及纵隔淋巴结,肉瘤样成分比例分别为100%和20%;疾病稳定(SD)7例,转移部位包括肺、淋巴结、肾上腺、骨和肝;疾病进展(PD)5例,总疾病控制率为64%.随访至2009年7月,出现PD 9例,PFS 6(0～19)个月.肉瘤样成分比例与治疗的客观反应及PFS均无相关性(P=0.247,P=0.554).结论 索拉非尼常规剂量治疗具有肉瘤样分化的转移性肾细胞癌有一定疗效,但客观有效率及PFS与肉瘤样成分的比例无明显相关性.     

靶向治疗时代转移性肾癌多学科综合治疗的单中心经验总结

目的总结在靶向药物治疗基础上单中心转移性肾癌的多学科诊疗经验。方法回顾性分析2007年12月至2019年2月中山大学肿瘤防治中心经多学科诊疗团队(multi-disciplinary team,MDT)诊治的168例转移性肾癌(metastatic renal cell,mRCC)患者的临床数据。根据治疗方式将患者分为3组。单纯靶向药物治疗(A组)76例,男55例,女21例;年龄52(17~73)岁;透明细胞癌60例,非透明细胞癌16例;国际转移性肾细胞癌联合数据库(International Metastatic Renal Cell Carcinoma Database consortium,IMDC)预后评分低危11例,中危48例,高危17例;初诊时即有转移44例;行原发灶切除术63例。靶向药物治疗+局部治疗(B组)66例,男55例,女11例;年龄54(21~86)岁;透明细胞癌49例,非透明细胞癌17例;IMDC预后评分低危13例,中危39例,高危14例;初诊时即有转移32例;行原发灶切除术56例。靶向药物治疗+局部治疗+免疫治疗(C组)26例,男19例,女7例;年龄52(23~83)岁;透明细胞癌15例,非透明细胞癌11例;IMDC预后评分低危9例,中危13例,高危4例;初诊时即有转移9例;行原发灶切除术26例。3组患者一般资料比较差异均无统计学意义(P>0.05)。一线靶向治疗药物为舒尼替尼、索拉非尼、阿昔替尼。舒尼替尼50 mg,每日1次,用药4周停2周;索拉非尼400 mg,每日2次;阿昔替尼5 mg,每日2次。接受舒尼替尼、索拉非尼、阿昔替尼一线治疗者分别为103、18、39例。靶向药物治疗时间均>6个月。免疫治疗采用派姆单抗(Pembrolizumab)2 mg/kg静脉应用,每3周1次,或低剂量(20 mg)派姆单抗孵育经体外扩增后的自体外周血树突状细胞细胞因子诱导杀伤细胞(dendritic cells cytokine induced killer,DC.CIK),每周1次,4次后改为每2周1次。18例采用DC.CIK,8例采用派姆单抗。局部治疗方式包括立体定向放疗(stereotactic body radiation therapy,SBRT)和外科治疗(手术切除或能量消融治疗)。根据靶向药物治疗效果,转移灶部位、数量、与周围器官关系,以及患者的意愿,经MDT专家讨论后决定局部治疗方式。92例接受局部治疗,其中单纯外科治疗34例,单纯SBRT 37例,外科治疗+SBRT 21例。比较3组的疗效和不良反应情况,分析不同治疗方法与患者总生存时间(overall survival,OS)的关系。结果168例中位随访23个月(6~117个月)。中位无进展生存时间(progression free-survival,PFS)为18.3个月,中位OS为33.5个月;2年生存率为66%,5年生存率为35%。A、B、C组的中位OS分别为29.8个月、44.6个月和未达,2年生存率分别为58%、67%和89%,5年生存率分别为12%、46%和57%。在靶向药物治疗的基础上接受联合治疗者的预后均优于单纯靶向药物治疗者,5年总OS分别为51%和11%。C组的中高危mRCC患者预后明显优于A、B组。在接受免疫治疗的患者中,靶向药物治疗联合DC.CIK与联合派姆单抗的中位OS分别为49.1个月和53.1个月,差异无统计学意义(P=0.541)。单因素分析结果显示,OS与IMDC评分、原发灶切除、治疗模式相关(P<0.05)。多因素分析结果显示,OS与治疗模式、原发灶切除显著相关(P<0.05),靶向药物治疗+免疫治疗+局部治疗可使mRCC患者死亡风险下降约60%(HR=0.39,95%CI 0.17~0.89,P=0.026)。78例使用靶向药物治疗发生3~4级不良反应,12例因无法耐受一线靶向药物治疗不良反应而停药或换药。16例采用靶向药物联合免疫治疗发生3~4级药物不良反应,主要为疲乏8例次、白细胞降低4例次、血小板降低3例次、转氨酶和胆红素升高3例次。靶向药物治疗联合DC.CIK治疗的严重不良反应发生例数少于联合派姆单抗治疗(6例与12例),特别是显著降低了血液学毒性(2例与5例)和肝毒性(0例与3例),差异均有统计学意义(P<0.05)。外科治疗后出现ClavienⅢ~Ⅳ级并发症16例次,主要为感染和切口延期愈合6例次、不全肠梗阻4例次,围手术期输血15例次。SBRT治疗后6例出现美国放射肿瘤协作组评分(Radiotherapy Oncology Group,RTOG)3级不良反应,其中骨髓抑制4例,皮肤反应和放射性神经炎2例,未观察到≥4级不良反应。结论在靶向药物治疗基础上联合免疫治疗和局部治疗的mRCC患者预后明显优于采用单纯靶向药物治疗的患者。经MDT诊疗的综合治疗可使mRCC患者生存获益。     

根据血药浓度监测结果个性化调整舒尼替尼方案对转移性肾癌的安全性和疗效

目的:探讨根据血药浓度监测结果个性化调整舒尼替尼方案对转移性肾癌患者的安全性和疗效。方法:回顾性分析2014年1月至2020年12月于四川大学华西医院接受舒尼替尼治疗的65例晚期转移性肾癌患者的临床资料,其中20例行血药浓度监测(监测组),45例为通过倾向性评分匹配的同期接受舒尼替尼治疗但未行血药浓度监测者(未监测组)...