舒尼替尼联合多靶点抗原肽自体免疫细胞治疗晚期转移性肾细胞癌的临床疗效及安全性

目的 探究舒尼替尼联合多靶点抗原肽自体免疫细胞技术（MASCT）治疗晚期转移性肾细胞癌（RCC）的临床疗效及安全性。方法 选取本院2016年1月—2017年1月收治的52例晚期转移性RCC患者,根据治疗方案的不同分为对照组（22例,采用MASCT治疗）和观察组（30例,采用舒尼替尼联合MASCT治疗）。对比两组患者的临床疗效,采用酶联免疫吸附法（ELISA）检测患者治疗前后白介素-17（IL-17）、血管内皮生长因子（VEGF）、低氧诱导因子-1α（HIF-1α）和血小板衍化生长因子（PDGF）的血清水平,计算肿瘤微血管密度（MVD）,并对比两组患者的无进展生存期（PFS）、总生存期（OS）及不良反应发生率。结果 观察组临床治疗有效率为86.7%,显著高于对照组的59.1%（P<0.05）。治疗后,两组患者血清IL-17、VEGF、HIF-1α及PDGF水平均显著降低,且观察组显著低于对照组（P<0.05）。治疗后,两组患者MVD均显著降低,且观察组显著低于对照组（P<0.05）。观察组患者PFS和OS均显著长于对照组（P<0.05）。两组患者恶心、呕吐、腹泻、乏力、便秘、面部水肿、脱发、高血压、白发、血小板减少、中性粒细胞减少、贫血、尿酸升高、甲状腺功能降低、谷丙转氨酶升高、口腔黏膜炎、皮肤色素脱失、皮肤黄染、手足综合征等不良反应发生率比较,差异均无统计学意义（P>0.05）。结论 舒尼替尼联合MASCT治疗晚期转移性RCC可提高临床治疗效果,降低相关血清肿瘤标志物水平,延长生存期,且不增加不良反应,具有一定的临床应用价值。     

索拉非尼和舒尼替尼在转移性肾癌患者中的应用效果对比

目的：比较索拉非尼和舒尼替尼在转移性肾癌患者中的应用效果。方法：选取2013年1月至2016年1月期间某院收治的132例转移性肾癌患者为研究对象,将患者依据随机数字表法分为A组和B组,各66例。A组患者给予索拉菲尼治疗,B组患者给予舒尼替尼治疗。比较2组患者的疾病控制、血液学毒性、不良反应和生存状况。结果：A组与B组患者的疾病控制率分别为87.88%和86.37%,差异无显著性（P > 0.05）。B组患者的白细胞减少、中性粒细胞减少、血小板减少、贫血、肌酸激酶升高、转氨酶升高发生率均高于A组患者,差异具有显著性（P < 0.05）。A组与B组患者高血压、皮疹、食欲不振、手足综合征、脱发的发生率比较差异无显著性（P > 0.05）。B组患者腹泻和疲乏发生率均高于A组患者,差异具有显著性（P < 0.05）。治疗后对患者随访2年,A组和B组患者疾病进展率分别为45.45%和40.90%,两组患者的疾病进展率、6个月、12个月和24个月生存率比较差异无显著性（P > 0.05）。结论：索拉非尼和舒尼替尼治疗转移性肾癌患者疾病控制率和生存率差异无显著性,给予患者索拉菲尼治疗血液学毒性较小,给予患者舒尼替尼治疗腹泻发生率较高,但均无严重不良反应。     

索拉非尼治疗转移性肾细胞癌的疗效及安全性研究

目的 评价索拉非尼治疗转移性肾癌的疗效及安全性.方法 转移性肾癌40例患者,均给予甲基磺酸索拉非尼片治疗,初始剂量为800 mg/d,2次/d,连续给药21 d,停药7d,观察疗效和不良反应,以及免疫组织化学检测结果.结果 40例患者中未见完全缓解（CR）和部分缓解（PR）;疾病稳定（SD） 32例（80.0％）和疾病进展（PD）8例（20.0％）;消化系统不良反应发生28例（70.0％）;间隙连接蛋白32（ Cx32）在局限性肾癌中表达阳性率为30.5％,明显低于转移性肾癌组织的1.2％（x2=8.123,P＜0.01）,Cx32表达与临床分期呈负相关（r=-0.419,P＜0.05）;肾癌组织中血管内皮生长因子（VEGF）蛋白表达的阳性率75.5％,明显高于正常肾组织的18.5％ （x2 =8.723,P＜0.01）;VEGF在局限性肾癌阳性表达率72.0％与转移性肾癌的89.1％差异无统计学意义（x2=1.978,P＞0.05）.结论 索拉非尼对晚期肾癌病情控制有较好的效果,是治疗转移性肾癌的新选择.     

35例肾移植患者他克莫司血药浓度监测分析

目的：分析肾移植患者不同时期他克莫司血药浓度与用药量的关系,为他克莫司的使用提供参考。方法对我院2013年4月～2014年3月35例肾移植患者进行长期血药浓度监测,统计分析术后时间、用药剂量等因素与他克莫司血药浓度的关系。结果35例肾移植患者血药浓度监测共计195次,血药浓度个体差异较大。肾移植手术1个月后,他克莫司用药剂量、血药浓度较高,超过1个月后血药浓度控制在4～8ng/mL较为理想。结论他克莫司治疗窗较窄,建议服药期间进行他克莫司血药浓度监测。     

Recommendations on managing lenvatinib and everolimus in patients with advanced or metastatic renal cell carcinoma

Introduction: There are several second-line treatment options for patients with renal cell carcinoma after first-line failure of a tyrosine kinase inhibitor, especially with the recent approvals of cabozantinib, nivolumab, and the lenvatinib plus everolimus combination. A lack of reliable biomarkers and an overall lack of prospective head-to-head comparisons make it a challenge to choose a second-line treatment in the clinic.

Areas covered: In this review/meta-opinion, we describe the safety profile of the lenvatinib plus everolimus combination in renal cell carcinoma. The combination of lenvatinib plus everolimus has achieved the highest rates of objective responses and the longest progression free and overall survival in cross-comparison trials. At the same time, the safety profile of this combination, including the rate of total and severe adverse events, the percentage of dose reductions required, and the rate of treatment discontinuation, was less favorable compared with available monotherapy options, suggesting that better management could help to maximize the activity of this combination while protecting patients from undue harm.

Expert opinion: Herein, we aim to postulate multidisciplinary recommendations on the advice to offer to patients and caregivers before starting treatment and how to manage the combination from the perspective of daily clinical practice.     

Phase II study of vinflunine in patients with metastatic renal cell carcinoma

Summary Purpose: An open-label, multicentre, non-comparative phase II trial to determine the response rate of intravenous vinflunine as first line chemotherapy in patients with metastatic renal cell carcinoma (RCC). Patients and methods: Patients with metastatic RCC were treated with vinflunine 350 mg/m² (n = 11) or 320 mg/m² (n = 22) administered intravenously every 21 days. Results: Out of 33 patients included in this study, one partial response was observed in the group treated at 350 mg/m² and none in the group receiving 320 mg/m² resulting in a response rate in this population of 9.1% (95% CI: 0.2–41.3). Median progression free survival was 5.6 months (95% CI: 2.8–14.4) for patients treated at 350 mg/m², and 3.3 months (95% CI: 1.6–6.4) for those treated at 320 mg/m².The median survival time was 10.4 months (95% CI: 6.8–12.4) for the whole study population. The principal toxicities were grade 3/4 neutropaenia —90.9% at 350 mg/m² and 68.1% at 320 mg/m², febrile neutropaenia was recorded in 3 patients (27.3%) at 350 mg/m² and in 5 patients (22.7%) at 320 mg/m². One episode of thromboembolic event was reported in 1 patient at each dose level. Conclusion: Vinflunine given intravenously once every 3 weeks has not shown any clinically relevant activity in the management of patients with metastatic renal cell carcinoma; tolerance of the treatment was better at a dose of 320 mg/m² than at 350 mg/m². Supported by Institute de Recherche Pierre Fabre Oncologie, Boulogne-Billancourt, France.     

转移性肾细胞癌药物治疗方法的研究

肾细胞癌在我国的发病率逐年升高,且对于放化疗不敏感,免疫治疗效果有限,尤其是转移性肾细胞癌的预后较差。该文就转移性肾细胞癌的药物治疗方案的作用机制、现状及展望进行综述。     

Lenvatinib for use in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy

Introduction: In patients with mRCC options for second line therapies, following progression on anti-angiogenic agents, that demonstrate a survival advantage in clinical trials have been limited. Recently a number of agents have demonstrated efficacy in this setting. Here in we profile one such therapy, the combination of lenvatinib and everolimus, and discuss the expanded options for therapy available in this setting.

Areas covered: In this review, we discuss current algorithms for treatment of mRCC in both the first-line and second-line setting. We discuss the recent addition of cabozantinib and nivolumab, in the second line setting, to the market. Lenvatinib’s pharmacology, clinical efficacy and toxicity profile is discussed. A comprehensive literature review was performed using PUBMED.

Expert commentary: The current treatment algorithms for mRCC will likely see significant change in the coming years. The addition of immunotherapy to our treatment options in mRCC is of particular importance. Future trials examining the use of immunotherapy, both as monotherapy and in combination with VEGF targeted therapy, will likely be a dominant influence in the therapeutic landscape of mRCC. Progress in terms of the rapid expansion of available active therapies in mRCC needs to be balanced with current deficiencies in terms of predictive biomarkers.     

他克莫司替代环孢霉素A后对肾移植术后患者血脂的影响

目的：探讨用他克莫司（FK506）替换环孢霉素A（CsA）后对肾移植术后患者血脂和移植肾功能的影响。方法：选择本院接受同种异体肾移植术后的41例患者作为研究对象,其中,男21例,女20例,平均（38.2±22.5）岁。针对临床上应用CsA的患者中出现的一些毒副作用,将这些患者用FK506替换治疗随访1年以上,监测血清肌酐（SCr）、尿素氮、血脂等生化指标的变化情况。结果：绝大多数受者血脂浓度显著降低,其中12例患者血脂水平已明显正常;肌酐和尿素氮清除率明显改善（P〈0.05）。结论：在某些情况下,用FK506替换CsA可以使心脑血管和肾功能得到改善,并使毒副作用减轻或消失,有助于提高肾移植的长期存活率。     

A comparison of the pharmacokinetics of tacrolimus and microemulsified cyclosporin in paediatric renal transplant recipients

Objective Our objective was to identify common factors that determine the dose of tacrolimus and microemulsified cyclosporin in paediatric renal transplant recipients.Methods The concentration profiles of tacrolimus and cyclosporin in blood were determined in 68 children who had received a renal transplant. To avoid disruption of therapy, measurements were made at 2-h intervals over an 8-h period during normal dosing regimens. Direct comparisons of the two drugs were made in 14 of the subjects who were switched from cyclosporin to tacrolimus.Results The ratio of peak to trough levels for tacrolimus was approximately twofold compared with over threefold for cyclosporin. Area under the curve (AUC) for tacrolimus remained relatively constant in each 2-h period of the dosage interval compared with the AUC for cyclosporin, which varied by over twofold in the same time period. In the 14 subjects who received both drugs, there was a poor correlation between C₂/C₀, C₂, t_1/2 and AUC for tacrolimus and cyclosporin in the same individual. In a multivariate analysis, there were no significant associations for tacrolimus concentrations, AUC or C₂/C₀ with age, gender, calcium-channel blocker, quinolone or statin. For cyclosporin, there was some association for AUC with gender and quinolone use and a weak association with calcium-channel blocker or statin use.Conclusions Tacrolimus and microemulsified cyclosporin display a wide intra- and inter-individual variation in pharmacokinetic properties in young subjects. In the case of absorption represented by the peak-trough ratios, the values for tacrolimus are significantly less than those obtained with cyclosporin. The pharmacokinetic parameters obtained for one of these agents is not predictive for the behaviour of the other in young renal transplant recipients.     

Evaluation of carboplatin (NSC 241240) in patients with recurrent or metastatic renal cell carcinoma

Summary Eighteen evaluable patients with metastatic or recurrent renal cell carcinoma were treated with carboplatin. Fourteen patients received 400 mg/m² as the initial dose, and four patients received reduced doses based on prior radiation therapy and/or elevated serum creatinine. No responses were seen. Median survival of these 18 patients was 8.3 months. Risk group status which previously has been identified as an important indicator of survival was predictive for survival in this study. Patients in the most favorable risk groups had a median survival of 21.2 months vs. 6.6 months for the most unfavorable risk groups. No lethal toxicities occurred with the administration of carboplatin; however, 66% of patients received doses of sufficient magnitude to cause severe or life threatening thrombocytopenia or anemia.Other participating institutions include: Fox Chase Cancer Center, Philadelphia, PA (CA-18281); Hackensack Medical Center, Hackensack, NJ; Hawaii Medical Association, Honolulu, HI; University of Minnesota; Minneapolis, MN (CA- 20365); Newark Beth Israel Medical Center, Newark, NJ; Our Lady of Lourdes Hospital, Binghamton, NY; University of Pittsburgh, Pittsburgh, PA (CA-18653); Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL (CA-25988); University of Pretoria, Pretoria, South Africa (CA-21692); Tufts New England Medical Center Hospital, Boston, MA (CA-07190)     

The effect of information on preferences for treatments of metastatic renal cell carcinoma

Objective: Limited information exists regarding the effect of uncertainty in outcomes on patient preferences for metastatic renal cell carcinoma (mRCC) treatments. This study tested the effect on patients’ preferences and willingness to tolerate toxicities when patients were provided with information about possible correlations between treatment-related toxicities and efficacy.

Research design and methods: Patients with self-reported RCC diagnosis completed an online survey. Respondents were randomly assigned to the information treatment (i.e. information about the possible correlation). Medicines were defined by progression-free survival (PFS), three toxicities potentially correlated with PFS, and one toxicity uncorrelated with PFS. Direct-elicitation questions measured willingness to tolerate the toxicities, preferences for medicines with higher toxicity but a higher chance of longer PFS, and preferences for medicines with higher toxicity during treatment and a 2 week dosing schedule break. A discrete-choice experiment (DCE) tested the effect of information on relative preferences for medication attributes.

Results: A total of 378 RCC patients completed the survey. Respondents who received the information reported greater willingness to accept more severe toxicities and preferred treatment with a higher chance of longer PFS but more severe toxicities. The DCE results were consistent with the hypothesis that the information increased willingness to tolerate toxicities; however, the results were only statistically significant for changes in fatigue (none to severe; p?<?0.05) and hypertension (none to manageable; p?<?0.05).

Limitations: Online recruitment through patient support groups may limit generalizability to the population of patients with mRCC who would be candidates for the targeted therapies.

Conclusions: The findings suggest that RCC patients have diverse preferences but may be willing to continue targeted therapies, even in the presence of severe toxicities, if there is a chance of improved clinical benefit. Physicians should provide patients with comprehensive information about medication features, including toxicities and efficacy (and their potential correlation), to improve compliance and optimize outcomes.     

Phase I trial of thalidomide and Interleukin-2 in patients with metastatic renal cell carcinoma

Summary Background: The treatment of advanced renal cell cancer remains unsatisfactory, therefore new combination regimens such as thalidomide and IL-2 are of interest. A phase I trial of SC IL-2 and oral thalidomide was performed to identify the toxicity, maximum tolerated dose (MTD) and preliminary clinical activity of this regimen. Methods: 33 patients with advanced/metastatic RCC were enrolled. An established 8-week outpatient schedule of subcutaneously administered IL-2 in escalating doses, days 1–5, for 6 weeks with a 2 week rest was utilized with daily oral thalidomide. Cohorts of 4–6 patients were treated at 4 dose levels. Results: Toxicity was moderate to severe and related to dose level. All patients developed fever, chills and fatigue. 29/33 patients developed ≤ Grade 2 desquamation of hands and feet and/or rash. Dose limiting toxicity (DLT) included Grade 3 neutropenia and pulmonary embolus. The maximum tolerated dose (MTD) of IL-2 and thalidomide was 9.0 MIU/m² SC days 1–5, weeks 1 to 6 and 100 mg po daily, respectively. A median of 2 cycles of therapy was administered (range 1–9). 2/33 patients responded (1 CR—prior IL-2 therapy, 1 PR—no prior therapy) with an overall response of 6% (95% CI, 1–20%). One minimal response was converted to a surgical CR (remains disease free at 24 + months). Conclusion: Outpatient administration of IL-2 and thalidomide is possible with acceptable toxicity. Further evaluation of this regimen is underway.     

藏族男性原发性小细胞肾癌一例并文献复习

目的 总结原发性小细胞肾癌（RSCC）的临床特点和诊治方法.方法 报道1例69岁藏族男性RSCC的临床、影像学及病理资料,结合文献复习对该病的临床特征和诊断治疗方法进行分析.结果 患者因左侧腰痛2个月及间歇性无痛性肉眼血尿1周就诊;CT扫描发现肿瘤位于左肾上极背侧,最大径7.5 cm,术前临床分期T2aN0M0.行经腹根治性肾切除术,术后恢复良好,未接受化疗.随访6个月无复发生存.收集到文献报道的RSCC患者56例.RSCC 55例患者平均发病年龄（55.5±1.2）岁,发病高峰年龄在50～ 70岁.男女比为1.15∶1.肿瘤中位直径10.0 cm.无转移者中位生存期17.0个月;转移者中位生存期8.0个月.结论 RSCC罕见,恶性程度高,预后差;术前诊断闲难,依靠切除或者穿刺组织病理学诊断.诊断时无转移者生存期优于有转移者.     

阿昔替尼单药或联合帕博利珠单抗治疗舒尼替尼治疗失败的伴肝转移肾细胞癌的疗效及安全性分析

目的 研究阿昔替尼单药或联合帕博利珠单抗治疗舒尼替尼治疗失败的伴肝转移肾细胞癌的疗效及安全性.方法 选取2018年1月—2020年5月南京医科大学第二附属医院和南京医科大学第四附属医院收治的26例肾细胞癌患者为研究对象.对照组13例接受阿昔替尼单药口服治疗,观察组13例接受阿昔替尼口服联合帕博利珠单抗治疗,比较两组患者...     

Phase II trial of lenalidomide in patients with metastatic renal cell carcinoma

Summary Lenalidomide (CC-5013) is a structural derivative of thalidomide, with antiangiogenic and immunomodulatory effects. Fourteen patients with metastatic renal cell carcinoma (RCC) were enrolled on a phase 2 trial of lenalidomide administered orally at 25 mg daily for 21 days followed by a rest period of 7 days. The best response was stable disease in eight patients (57%) of the 14 evaluable patients. Toxicities included fatigue, hyperglycemia, dyspnea, and myelosuppression with decreased hemoglobin, lymphopenia, and neutropenia. Lenalidomide is tolerable, but no objective responses were observed in this clinical trial.