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.     

舍曲林个体化治疗原发性早泄的疗效分析

目的 比较不同剂量舍曲林治疗原发性早泄的临床疗效.方法选择86例符合原发性早泄诊断的患者,治疗前评估国际勃起功能评分表、中国早泄患者性功能评价表.第一阶段治疗4周,每日服用盐酸舍曲林50 mg并配合行为疗法.4周后,根据疗效和不良反应将患者分为3组进入第二阶段治疗4周:有效且无或有轻微不良反应者继续原治疗;无效但无明显不良反应者,舍曲林剂量凋整为每日100 mg;有效但有明显不良反应者舍曲林剂量调整为每日25 mg;无效且有明显不良反应、不能耐受者退出观察.结果86例第一阶段4周治疗后,有效63例(73.3%),无效23例(26.7%).其中,无明显不良反应53例(61.6%),有不良反应33例(38.4%).第二阶段治疗中,有效组中35例无明显不良反应和12例有轻微不良反应者继续原治疗,16例有明显不良反应且不能耐受者舍曲林剂量调整为每日25 mg.无效组中,18例无明显不良反应者将舍曲林剂量凋整为每日100 mg,5例退出观察.8周治疗后,50 mg组47例均有效,无明显不良反应;25 mg组中有效10例,无效6例,2例有轻微不良反应且可耐受;100 mg组中有效8例(44.4%),13例(72.2%)有不良反应但可以耐受,2例因明显不良反应退出治疗,1例无效且无明显不良反应.8周总有效率80.2%(65/81),总不良反应发生率21.0%(17/81).结论舍曲林治疗原发性早泄安全有效,个体化治疗方案有效率无明显变化,不良反应发生率显著降低,患者对治疗的依从性增加.

Abstract：

Objective To compare the therapeutic effects with different dosages of sertraline on patients suffering from idiopathic premature ejaculation. Methods IIEF-5 and CIPE questionnaires were completed before the treatment, and 86 patients who met the diagnostic standard of idiopathic premature ejaculation were finally recruited. Subjects were administered sertraline 50 mg/d combined with behavior therapy at stage Ⅰ for 4 weeks. Then, according to the therapeutic effects and the adverse events, all of the patients were divided into 3 groups for stage Ⅱ (another 4 weeks) as ①subjects with good effectiveness but with no or slight adverse events,would continue the treatments ②subjects with no therapeutic effects and with no obvious adverse events were allowed to increase the dosage of sertraline to 100 mg/d;③patients with effectiveness and obvious adverse events were al follows:lowed to reduce the dosage of sertraline to 25 mg/d. Those who had obvious adverse events and no effectiveness quit the study. Results During stage Ⅰ , 63 of 86 patients were effective (73.3%), and 23 patients had no improvement (26. 7%). Thirty-three patients had adverse events (38. 4%), and the remaining 53 patients had no obvious adverse events (61.6%). During stage Ⅱ , of the patients that responded to treatment, 35 patients who had no adverse events and 12 who had slight adverse events continued the treatment. Furthermore, 16 with intolerable adverse events were allowed to reduce the dosage to 25 mg/d. Meanwhile, of those without improvement, 18 subjects without obviousadverse events were allowed to increase the dosage to 100 mg/d, and 5 patients discontinued the treatment. Eight weeks later, among the patients taking 50 mg/d, 47 subjects were effectively with no obvious adverse events. Among the patients taking 25 mg/d, 10 showed improvement, 6 showed no improvement, and 2 had tolerable slight adverse events. Among the patients taking sertraline 100 mg/d,8 witnessed effectiveness, 13 had tolerable adverse events and 2 discontinued the treatment, with 1 having neither effectiveness nor obvious adverse events. The adverse events rate was 21.0% and the total effective rate of 8 weeks of treatment was 80.2 %. Conclusions Sertraline administration is an effective and safe way to treat idiopathic premature ejaculation. Although the effectiveness of the individualized treatment had no obvious improvement comparing routine therapy, there was a notable reduction in the adverse events rate, which increased the patient compliance.     

肾移植后因免疫抑制剂的不良反应转换应用咪唑立宾的效果

目的 探讨肾移植术后因不良反应而将吗替麦考酚酯(MMF)或硫唑嘌呤(Aza)转换为咪唑立宾(MZR)的有效性和安全性.方法 56例肾移植受者术后发生肺部感染23例,骨髓抑制14例,肝功能损害6例,腹泻13例.所有患者均采用以钙调磷酸酶抑制剂(CNI)+MMF(或Aza)+泼尼松(Pred)的免疫抑制方案,出现不良反应时,转换应用了CNI+MZR+Pred.转换治疗后随访(33.2±17.4)个月(11～53个月),观察转换治疗后的效果和不良反应.结果 转换治疗后,23例肺部感染的患者,1例再次出现肺部感染,死于心、肺功能衰竭,其余均未再出现肺部感染;骨髓抑制的14例患者中,13例血常规恢复正常,1例未恢复;肝功能损害的6例患者经转换治疗后,肝功能均恢复正常;13例腹泻患者的症状均缓解.转换前,患者血清肌酐为(123±21.3)μmol/L,转换后,血清肌酐为(119±18.2)μmol/L,二者比较,差异无统计学意义(P＞0.05).转换治疗后,有1例(1.7%)患者发生排斥反应,9例(16.1%)出现不同程度的血尿酸升高,1例出现指(趾)关节疼痛等症状,均经对症治疗后好转.结论 在肾移植术后发生免疫抑制剂不良反应时,转换应用咪唑立宾效果良好,安全性高,为肾移植后患者的个体化免疫抑制方案的应用提供一种新的选择.

Abstract：

Objective To investigate the efficacy and safety of conversion therapy to mizoribine (MZR) for renal transplant patients who suffered MMF or Aza adverse reaction. Methods In 56 patients with adverse reactions at different time points after renal transplantation, there were 23 cases of pulmonary infection, 14 cases of bone marrow depression, 6 cases of hepatic functional lesion and 13 cases of diarrhea. The immunosuppressive protocols of these patients were changed to CNI + MZR + Pre when the adverse reaction occurred. During the follow-up period (11 to 53 months), the effect and adverse events of conversion treatment were observed. Results After conversion treatment, 1 of 23 patients with pulmonary infection was re-infected after 26 months and finally died of heart and lung function failure. In 14 patients with bone marrow depression, blood test returned to normal in 13cases. Six patients with hepatic functional lesion were administered hepatoprotection treatment and their liver function was restored without recurrence of impaired liver function. All 13 patients with diarrhea were relieved without recurrence. The serum creatinine was 123 ± 21.3 μmol/L and 119±18. 2 μmol/L before and after the conversion therapy respectively (P＞0. 05). During the follow-up period, all patients' graft function was good. The incidence of rejection was 1.7 % (1 case). Nine patients (16. 1 %) had a higher level of uric acid after conversion. One patient had finger and toe joint pain. The symptoms were relieved after symptomatic treatment. Conclusion There were high security and good effect of conversion therapy to MZR due to MMF or Aza adverse reaction. Besides, MZR conversion therapy for renal transplantation patients provided a new option for individual immunosuppression.     

肾移植后因免疫抑制剂的不良反应转换应用咪唑立宾的效果

Objective To investigate the efficacy and safety of conversion therapy to mizoribine (MZR) for renal transplant patients who suffered MMF or Aza adverse reaction. Methods In 56 patients with adverse reactions at different time points after renal transplantation, there were 23 cases of pulmonary infection, 14 cases of bone marrow depression, 6 cases of hepatic functional lesion and 13 cases of diarrhea. The immunosuppressive protocols of these patients were changed to CNI + MZR + Pre when the adverse reaction occurred. During the follow-up period (11 to 53 months), the effect and adverse events of conversion treatment were observed. Results After conversion treatment, 1 of 23 patients with pulmonary infection was re-infected after 26 months and finally died of heart and lung function failure. In 14 patients with bone marrow depression, blood test returned to normal in 13cases. Six patients with hepatic functional lesion were administered hepatoprotection treatment and their liver function was restored without recurrence of impaired liver function. All 13 patients with diarrhea were relieved without recurrence. The serum creatinine was 123 ± 21.3 μmol/L and 119±18. 2 μmol/L before and after the conversion therapy respectively (P＞0. 05). During the follow-up period, all patients' graft function was good. The incidence of rejection was 1.7 % (1 case). Nine patients (16. 1 %) had a higher level of uric acid after conversion. One patient had finger and toe joint pain. The symptoms were relieved after symptomatic treatment. Conclusion There were high security and good effect of conversion therapy to MZR due to MMF or Aza adverse reaction. Besides, MZR conversion therapy for renal transplantation patients provided a new option for individual immunosuppression.     

肾移植后因免疫抑制剂的不良反应转换应用咪唑立宾的效果

Objective To investigate the efficacy and safety of conversion therapy to mizoribine (MZR) for renal transplant patients who suffered MMF or Aza adverse reaction. Methods In 56 patients with adverse reactions at different time points after renal transplantation, there were 23 cases of pulmonary infection, 14 cases of bone marrow depression, 6 cases of hepatic functional lesion and 13 cases of diarrhea. The immunosuppressive protocols of these patients were changed to CNI + MZR + Pre when the adverse reaction occurred. During the follow-up period (11 to 53 months), the effect and adverse events of conversion treatment were observed. Results After conversion treatment, 1 of 23 patients with pulmonary infection was re-infected after 26 months and finally died of heart and lung function failure. In 14 patients with bone marrow depression, blood test returned to normal in 13cases. Six patients with hepatic functional lesion were administered hepatoprotection treatment and their liver function was restored without recurrence of impaired liver function. All 13 patients with diarrhea were relieved without recurrence. The serum creatinine was 123 ± 21.3 μmol/L and 119±18. 2 μmol/L before and after the conversion therapy respectively (P＞0. 05). During the follow-up period, all patients' graft function was good. The incidence of rejection was 1.7 % (1 case). Nine patients (16. 1 %) had a higher level of uric acid after conversion. One patient had finger and toe joint pain. The symptoms were relieved after symptomatic treatment. Conclusion There were high security and good effect of conversion therapy to MZR due to MMF or Aza adverse reaction. Besides, MZR conversion therapy for renal transplantation patients provided a new option for individual immunosuppression.     

肾移植后因免疫抑制剂的不良反应转换应用咪唑立宾的效果

Objective To investigate the efficacy and safety of conversion therapy to mizoribine (MZR) for renal transplant patients who suffered MMF or Aza adverse reaction. Methods In 56 patients with adverse reactions at different time points after renal transplantation, there were 23 cases of pulmonary infection, 14 cases of bone marrow depression, 6 cases of hepatic functional lesion and 13 cases of diarrhea. The immunosuppressive protocols of these patients were changed to CNI + MZR + Pre when the adverse reaction occurred. During the follow-up period (11 to 53 months), the effect and adverse events of conversion treatment were observed. Results After conversion treatment, 1 of 23 patients with pulmonary infection was re-infected after 26 months and finally died of heart and lung function failure. In 14 patients with bone marrow depression, blood test returned to normal in 13cases. Six patients with hepatic functional lesion were administered hepatoprotection treatment and their liver function was restored without recurrence of impaired liver function. All 13 patients with diarrhea were relieved without recurrence. The serum creatinine was 123 ± 21.3 μmol/L and 119±18. 2 μmol/L before and after the conversion therapy respectively (P＞0. 05). During the follow-up period, all patients' graft function was good. The incidence of rejection was 1.7 % (1 case). Nine patients (16. 1 %) had a higher level of uric acid after conversion. One patient had finger and toe joint pain. The symptoms were relieved after symptomatic treatment. Conclusion There were high security and good effect of conversion therapy to MZR due to MMF or Aza adverse reaction. Besides, MZR conversion therapy for renal transplantation patients provided a new option for individual immunosuppression.     

美多巴治疗早期非创伤性股骨头坏死的近期疗效观察

Objective To observe the preliminary effects of the treatment for early non-traumatic osteonecrosis of the femoral head with Madopar. Methods Thirty-one patients with 48 hips of early stage (Ficat Ⅰ,Ⅱ) non-traumatic necrosis of the femoral head were treated with oral administration of Madopar since 2002. The disease was associated with consumption of alcohol in 16 cases with 27 hips; use of steroids in 10 cases with 13 hips; both consumption of alcohol and use of steroids in 2 cases with 4 hips; the remaining 3 cases, the condition was idiopathic. According to the criteria of Ficat et al., there were 4 hips in stage Ⅰ; 40 in stage Ⅱa and 4 in stage Ⅱb. Eighteen patients had received madopar for 10-28 months; 13 patients had been receiving the drug until now. Follow-up examinations were made by radiography, MRI and Charnley modified Merle d'Aubigne score. Results All patients were followed up for 12-84 months (average 27.8 months). The clinical symptoms improved in all cases. X-ray films showed that the bone density increased in nearly all the femoral heads, and 68.75%(33/48) of them maintained their shapes. The follow-up MRI showed their necrotic indices had decreased. The rate of clinical satisfaction was 91.67%(44/48), and the successful rate of treatment was 72.92%(35/48), and the collapse rate of early stage necrosis of the femoral head is 27.08%(13/48). Conclusion The preliminary results showed that madopar could prevent or delay collapse of the femoral head in early stage of osteonecrosis.     

美多巴治疗早期非创伤性股骨头坏死的近期疗效观察

Objective To observe the preliminary effects of the treatment for early non-traumatic osteonecrosis of the femoral head with Madopar. Methods Thirty-one patients with 48 hips of early stage (Ficat Ⅰ,Ⅱ) non-traumatic necrosis of the femoral head were treated with oral administration of Madopar since 2002. The disease was associated with consumption of alcohol in 16 cases with 27 hips; use of steroids in 10 cases with 13 hips; both consumption of alcohol and use of steroids in 2 cases with 4 hips; the remaining 3 cases, the condition was idiopathic. According to the criteria of Ficat et al., there were 4 hips in stage Ⅰ; 40 in stage Ⅱa and 4 in stage Ⅱb. Eighteen patients had received madopar for 10-28 months; 13 patients had been receiving the drug until now. Follow-up examinations were made by radiography, MRI and Charnley modified Merle d'Aubigne score. Results All patients were followed up for 12-84 months (average 27.8 months). The clinical symptoms improved in all cases. X-ray films showed that the bone density increased in nearly all the femoral heads, and 68.75%(33/48) of them maintained their shapes. The follow-up MRI showed their necrotic indices had decreased. The rate of clinical satisfaction was 91.67%(44/48), and the successful rate of treatment was 72.92%(35/48), and the collapse rate of early stage necrosis of the femoral head is 27.08%(13/48). Conclusion The preliminary results showed that madopar could prevent or delay collapse of the femoral head in early stage of osteonecrosis.     

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.     

舒尼替尼治疗晚期肾癌的临床疗效及安全性分析

目的 初步探究舒尼替尼治疗晚期肾癌的疗效及安全性.方法 回顾性分析我科38例接受舒尼替尼治疗的晚期肾癌患者的临床资料.38例中男27例,女11例;行肾癌根治术34例,行保留肾单位手术1例,3例未行手术治疗.病理类型:透明细胞癌31例、乳头状癌3例、嫌色细胞癌1例、混合细胞癌3例.转移部位:肺21例、淋巴结9例、肝2例、骨5例、肾上腺2例、腔静脉10例、附件1例、腹膜后7例,其中单发转移20例(52.6%),多发转移18例(47.4%).舒尼替尼治疗采用标准的4/2方案:50 mg/d,口服,服4周停2周.结果 38例患者的疗效评价:完全缓解2例(5.4%)、部分缓解5例(13.1%)、疾病稳定26例(68.4%)、疾病进展5例(13.1%);客观缓解率18.5%,疾病控制率86.9%.中位无进展生存期为15个月,中位总生存期为22个月.常见不良反应有中性粒细胞降低、手足反应、口腔黏膜溃疡、皮肤黄染、毛发变白、腹泻、乏力和高血压.结论 舒尼替尼治疗晚期肾癌具有良好的效果,患者临床获益明显.虽然不良反应较多,但多为Ⅰ或Ⅱ级,在患者耐受范围之内.     

Commentary on “Cytoreductive radiofrequency ablation in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with sunitinib or interferon-α.” Tsimafeyeu I,Zart JS,Chung B,Kidney Cancer Research Bureau,Moscow, Russian Federation.: BJU Int 2013; 112(1):32–8. [Epub 2013 Jun 7]. doi: 10.1111/bju.12107.

ObjectivesTo evaluate the role of cytoreductive radiofrequency ablation (cRFA) in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with immuno- or targeted therapy. To assess the efficacy of sunitinib in patients with metastatic RCC with unresected small primary tumours.Patients and methodsThree parallel single-arm prospective studies were conducted. Eligibility criteria were nearly identical for all trials and included: histopathologically confirmed RCC; metastatic measurable disease; size of primary tumour <5 cm; good or intermediate prognosis according to the Memorial Sloan-Kettering Cancer Center model; and no previous therapy. Study 1: Patients were treated with percutaneous cRFA under computed tomography guidance followed by interferon (IFN)-α, 9 MIU, s.c., three times per week. Study 2: Patients received cRFA followed by sunitinib in repeated 6-week cycles of 50 mg/day orally for 4 weeks, then 2 weeks off treatment. Study 3: Patients with unresected primary RCC received sunitinib alone. The primary endpoint was progression-free survival (PFS).ResultsBaseline patient characteristics (age, gender, histology, Eastern Cooperative Oncology Group performance status, metastatic sites, primary tumour size) were similar in all three studies. Efficacy data for 114 evaluable patients showed an objective response rate of 8% (95% confidence interval [CI] 4.5, 10.5) for study 1, 28.9% (95% CI 15.2, 34) for study 2, and 31.6% (95% CI 20.3, 38.9) for study 3. The median (95% CI) PFS times were 9.1 (6.9, 10.2), 13.4 (9.8, 14.4) and 12.7 (11.3, 13.5) months for studies 1, 2 and 3, respectively. Objective response rate was significantly higher and PFS significantly longer in the sunitinib trials than in study 1 (P<0.01 all differences); no differences were found between studies 2 and 3 (objective response rate, P = 0.1; PFS, P = 0.6). Study 1 met its primary endpoint, showing that PFS was significantly longer than the expected 5 months (P = 0.02). The median (95% CI) objective survival (OS) times were greater in study 2 (cRFA/sunitinib) and study 3 (sunitinib-alone) than in study 1 (IFN-α) at 27.2 (22.6, 31.8) and 22.5 (20.7, 24.3) vs 19.5 (16.3, 22.7) months, respectively. Differences were significant (study 1 vs 2, hazard ratio [HR] = 0.55; P = 0.003; study 1 vs study 3 HR = 0.6, P = 0.01). OS was significantly longer in the cRFA/sunitinib group compared with the sunitinib-alone group (HR = 0.71; P = 0.04). There were no unexpected toxicities of medical treatment or complications of cRFA.ConclusionscRFA is a safe and effective approach for select patients with metastatic RCC treated with immunotherapy. The cRFA technique did not improve PFS in patients treated with sunitinib; cRFA probably has impact on OS in these patients. This needs to be tested in a larger trial. Sunitinib was effective in patients with metastatic RCC with unresected small primary tumours.     

Clinical efficacy and prognostic factors for overall survival in Japanese patients with metastatic renal cell cancer treated with sunitinib

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? A randomized prospective phase III clinical trial for systemic treatment‐naïve metastatic renal cell cancer (RCC) patients demonstrated the superiority of sunitinib over interferon with an acceptable safety profile. However, a commonly asked question is whether patients with RCC in clinical trials are representative of those with this disease being seen in ordinary clinical practice. To our knowledge, this is the first report of sunitinib for the Japanese patients with metastatic RCC in ordinary clinical practice. The estimated median PFS and OS in this study were 9.3 and 32.2 months, respectively. The application of the MSKCC model distinctly separated OS curves (P < 0.001), suggesting that MSKCC prognostic factors might be still valid to predict survival in metastatic RCC in the era of molecular targeted therapy.

OBJECTIVES

• ? To report the treatment efficacy and safety profile of sunitinib for patients with metastatic renal cell carcinoma (RCC) in ordinary clinical practice.
• ? In addition, to investigate the prognostic clinicopathological factors in these patients.

PATIENTS AND METHODS

• ? The present study consisted of native Japanese patients with metastatic RCC, comprising 29 pretreated and 34 systemic treatment‐naïve patients.
• ? Univariate and multivariate analyses were performed by the log‐rank test and the Cox proportional hazards model, respectively.

RESULTS

• ? Estimated median progression‐free survival and overall survival (OS) were 9.3 months (95% confidence interval, CI, 5.0–13.7) and 32.2 months (95% CI, 24.4–40.0), respectively.
• ? Among the patients pretreated before sunitinib, two patients were treated with initialized systemic therapy with sorafenib and the remaining 27 were initialized with interferon‐α.
• ? The OS from the initial systemic therapy of the patients in pretreated groups was 79.6 months (95% CI, 14.6–144.5).
• ? The application of the Memorial Sloan‐Kettering Cancer Center model distinctly separated the OS curves (P < 0.001).
• ? The most common grade 3 adverse events were fatigue (53%), thrombocytopaenia (48%), hand‐foot syndrome (16%), anaemia (20%), hypertension (10%) and leucopaenia (9%), although these events were manageable and reversible.

CONCLUSIONS

• ? Sunitinib has a favourable efficacy/safety profile for Japanese metastatic RCC patients in clinical practice.
• ? The estimated median OS was >2 years with acceptable tolerability.
• ? The median OS from the initial systemic therapy of the pretreated patients was >6 years.
• ? Memorial Sloan‐Kettering Cancer Center prognostic factors still appear to be valid for predicting survival in metastatic RCC in the era of molecular targeted therapy.

     

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.     

索拉非尼联合干扰素α一线治疗晚期肾癌Ⅳ期临床试验中期分析

目的 观察索拉非尼联合干扰素α(IFN-α)作为一线方案治疗晚期肾癌的疗效与安全性.方法 本研究为多中心、非随机Ⅳ期临床试验.入组初治的晚期肾癌137例.男102例,女35例.中位年龄56(18～81)岁.索拉非尼400 mg口服,2次/d;IFN-α 300万U,皮下注射,5次/周(d1～5),持续治疗,直至患者不能耐受或出现疾病进展.评价客观反应率、临床获益率、不良反应发生率.结果 完全缓解2例(1.5%),部分缓解43例(31.4%),客观有效率32.8%(45/137).截止到2009年2月底,中位随访时间11.9个月,疾病进展25例,中位无疾病进展时间尚未达到.常见不良反应为手足皮肤反应66例(48.2%)、脱发32例(23.4%)、皮疹28例(20.4%)、腹泻27例(19.7%)、发热23例(16.8%)、疲乏14例(10.2%),其中3～4级手足皮肤反应12例(8.8%).结论 索拉非尼联合IFN-α治疗晚期肾癌有效率32.8%,安全性良好,可作为晚期肾癌的一线治疗方案.     

Systemic therapy for chromophobe renal cell carcinoma: A systematic review

Background: Chromophobe renal cell carcinoma (chRCC) subtype accounts for almost 5% of total RCC cases. It carries the best prognosis among the rest of RCC types. However, patients with metastatic chRCC disease have worse prognosis than patients with advanced clear cell RCC. Furthermore, available data regarding systemic therapy for chRCC patients are scarce and confusing. Aim: The aim of this systematic review is to search for and critically appraise studies that investigate the results of systemic therapies in patients diagnosed with metastatic chRCC disease. Methods: Search strategy included PUBMED, CENTRAL, clinicaltrials.gov databases, and abstracts of major conferences with a focus on urologic oncology (till March 2019). Studies investigating patients that were treated with systemic therapy for advanced chRCC disease were included. Primary outcomes were progression-free survival and objective response rate. Secondary outcome was overall survival. Screening of available studies was carried out by 2 groups of reviewers, as well as the quality assessment of the included studies. Results: The systematic search yielded 369 studies, of which 15 studies (2 randomized control trials and 13 cohort studies), involving 183 patients, met the eligibility criteria. The 2 randomized control trials that directly compared sunitinib vs. everolimus, suggested an advantage for sunitinib without being statistically significant. Furthermore, sunitinib seems to be superior than sorafenib at least in terms of objective response rate. Regarding mTOR inhibitors, they may have a role in a specific subset of chRCC patients, that needs to be further explored. Finally, as far as immunotherapy is concerned, available data suggest that chRCC seems to be resistant to recent immune check point inhibitors, since just a few tumor responses were observed with the administered immunotherapy regiments. Conclusion: The optimum therapy for metastatic chRCC is still missing, as results from ongoing trials are awaited. More studies, of high quality and adequate sample size, that will be based on the specific biology of chRCC, have to be carried out in order to identify the best treatment.     

An adult Xp11.2 translocation renal carcinoma showing response to treatment with sunitinib

A rare variant of renal cell carcinoma (RCC) with a translocation involving Xp11.2 has become increasingly recognized as a separate entity in the 2004 World Health Organization (WHO) kidney carcinoma classification. These tumors predominantly affect children and young adults and tend to present with advanced stage disease. Although reported to be indolent in children, adult cases run a more aggressive course. Little is known about their natural history, prognosis and response to therapy.We report a case of Xp11 translocation renal cancer in a 33-year-old male patient who presented with widespread rapidly progressive metastatic disease involving extensive intra-thoracic lymph nodes, supra-clavicular, retroperitoneal lymph nodes, lung nodules, and peritoneal mass.He had failed to respond to treatment with high dose interleukin 2, but showed a significant clinical response to treatment with the multikinase inhibitor sunitinib. CT scan performed after 3 cycles (18 weeks) of therapy revealed more than 65% reduction of measurable disease by response evaluation criteria in solid tumors (RECIST) criteria, resolution of other assessable lesions, and a clinical benefit that lasted for over 13 months. But unfortunately, this was subsequently followed by a rapidly progressive course.The well-recognized clinical efficacy of multikinase inhibitors such as sunitinib and sorafenib is based on the outcomes in patients with clear cell histology. There is limited data on efficacy in non-clear cell RCC, but activity in translocation RCC has not been reported. To our knowledge, this is the first documented case of Xp11 translocation carcinoma to have demonstrated an objective durable response to sunitinib. It remains unclear how resistance to sunitinib develops, but the results to date support further evaluation of sunitinib in cases of translocation RCC.