MASTERPLAN: study of the role of nurse practitioners in a multifactorial intervention to reduce cardiovascular risk in chronic kidney disease patients

Moderate to severe chronic kidney disease (CKD) is associated with increased cardiovascular risk. Usually nephrologists are primarily responsible for the care of CKD patients. However, in many cases treatment goals, as formulated in guidelines, are not met. The addition of a nurse practitioner might improve the quality of care. The Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study is a randomized controlled multicenter trial, aimed at investigating whether a multifactorial approach in patients with moderate to severe CKD (stage 3 and 4) to achieving treatment goals using both a polydrug strategy and lifestyle treatment either with or without the addition of a nurse practitioner will reduce cardiovascular risk and slow the decline of kidney function. Patients (n=793) have been randomized to nurse care or physician care. In the nurse-care arm of the study, nurse practitioners use flowcharts to address risk factors requiring drug and/or lifestyle modification. They have been trained to coach patients by motivational interviewing with the aim of improving patient self-management. At baseline, both treatment groups show equal distributions with regard to key variables in the study. Moreover, in only 1 patient were all risk factors within the limits as defined in various guidelines, which underscores the relevance of our initiative.     

The safety and efficacy of PCNL with supracostal approach in the treatment of renal stones

Objective  

Supracostal superior calyceal access has been shown to be the most suitable approach for staghorn calculi, calculi in the upper ureter, and complex inferior calyceal calculi. It is a good choice for direct access for most of the intrarenal collecting system and upper ureter. The aim of this retrospective study was to evaluate a single center data regarding the safety and efficacy of this approach for percutaneous renal stone surgery.     

Comparison of efficacy of roxadustat and erythropoietin for the treatment of renal anemia in patients with chronic kidney disease: a retrospective study

BackgroundRenal anemia is a common complication in patients with end-stage renal disease (ESRD). Both roxadustat and recombinant human erythropoietin (rhEPO) are alternative option for patients with renal anemia. However, the adverse events of rhEPO limited the wide use of it and the concrete difference of real clinical efficacy of rhEPO and roxadustat was still uncertain. This study aimed to assess the clinical efficacy of roxadustat for improving renal anemia in patients with chronic kidney disease.MethodsA retrospective cohort study of 790 consecutive patients with renal anemia treated with roxadustat and rhEPO was conducted at the Zhejiang Provincial People’s Hospital. Patients were classified into two groups: roxadustat (n=95) and rhEPO (n=695). Baseline characteristics were compared in two groups. After propensity-score matching at a 1:3 ratio, we compared the efficacy of roxadustat and rhEPO in improving anemia, mainly using the Mann-Whitney U test. The follow-up period lasted 24 weeks.ResultsThe baseline characteristics were comparable between the two groups after propensity-score matching. There were no significant differences in the hemoglobin levels and estimated glomerular filtration rates (eGFRs) of the two groups before roxadustat or rhEPO treatment (P>0.05). The hemoglobin level after 4 weeks of treatment was 96 g/L in the roxadustat group, and the increase from baseline was 10 g/L; in the rhEPO group, these values were 87 and 6 g/L, respectively (P<0.001). After 12 weeks of treatment, the hemoglobin level and change from baseline were 105 and 15 g/L in the roxadustat group and 94 and 11 g/L in the rhEPO group, respectively (P<0.001). Similar results were observed after 24 weeks of treatment; the hemoglobin level and change from baseline were 105 and 17 g/L in the roxadustat group and 97 and 14 g/L in the rhEPO group (P=0.001).ConclusionsThis retrospective study demonstrated that orally administered roxadustat improved hemoglobin levels more than rhEPO in patients with CKD and anemia.     

Long-term efficacy of hyperuricaemia treatment in renal transplant patients.

BACKGROUND: Although hyperuricaemia and gout are frequently found in renal transplant recipients, little has been published on the efficacy of urate-lowering therapy (ULT) in this patient population. We therefore examine the effects of allopurinol and benziodarone therapy in a cohort of renal transplant patients. METHODS: We reviewed files from a cohort of 1328 patients that received renal transplantation. The selection criteria included: functioning allograft, hyperuricaemia for >12 months or gout, ULT lasting at least 1 year and at least two control measurements after the onset of ULT. Patients on azathioprine were treated with benziodarone to avoid azathioprine-allopurinol interactions. RESULTS: Two-hundred and seventy-nine patients fulfilled the criteria for review. They were treated with 289 courses of ULT: 100 with allopurinol (mean dose: 376 mg/day/dl/min of creatinine clearance) and 189 with benziodarone (mean dose: 73 mg/day). The mean follow-up was 38 months. Both drugs were effective for the control of hyperuricaemia, but benziodarone caused greater reductions in serum uric acid levels, especially when used at mean doses of >75 mg/day. Severe side effects were uncommon, in both the allopurinol and benziodarone groups. CONCLUSIONS: Both allopurinol and benziodarone were effective for the control of hyperuricaemia in renal transplantation. Benziodarone at doses >75 mg/day was more effective than allopurinol in reducing serum uric acid levels and also reduced the risk of azathioprine-allopurinol interactions.     

Indications and efficacy of parathyroidectomy in the treatment of secondary hyperparathyroidism in patients with chronic renal failure: our experience

Although secondary hyperparathyroidism is improved by pharmacological therapy; 10-30% of patients with chronic renal failure undergo parathyroidectomy. The authors report on their experience with 66 cases of secondary hyperparathyroidism surgically treated over the period from January 1991 to December 2002. The surgical indications included: persistent hypercalcaemia, osteodystrophy with bone fractures, joint pain, itching and ectopic calcifications. The median preoperative parathyroid hormone level was 400 pg/ml. The operations performed were: subtotal parathyroidectomy (PTX 7/8) in 43 cases; total parathyroidectomy with autotransplantation (PTXt + At) in 13 cases; total parathyroidectomy (PTXt) alone in 6 cases and incomplete parathyroidectomy (PTXi) in 4 cases. The immediate results were satisfactory in each group. Calcium levels reverted to normal 24-48 hours postoperatively in 37 patients with PTX 7/8, in 11 patients with PTXt + At, in 5 patients with PTXt; 4 patients with PTXi showed a reduction, but no normalization, of calcium levels. Almost all patients, except those undergoing PTXi, showed an acceptable reduction in PTH levels in 25-35 days. Secondary hyperparathyroidism relapsed in 3 cases with PTXt + At and in 2 cases with PTX 7/8, while it proved persistent in 50% of patients with PTXi and in 7% of patients with PTX 7/8. Patients with PTXt mainly showed a substantial reduction of calcium levels. Parathyroidectomy is indispensable for the treatment of secondary hyper-parathyroidism. In our opinion, PTX 7/8 is the surgical treatment of choice because it is the easiest technique to perform and has the lowest relapse rate.     

Rationale and design of oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents,darbepoetiN alfa (BRIGHTEN Trial)

Background

Renal anemia is an important complication in non-dialysis chronic kidney disease (CKD) patients as well as in dialysis patients. Although recombinant human erythropoietin has dramatically improved prognosis and quality of life in these patients, there have been issues among non-dialysis CKD patients who exhibit hyporesponsiveness to erythropoiesis-stimulating agent (ESA). The causes and definition of ESA hyporesponsiveness, as well as the incidence of renal and cardiovascular disease (CVD) events in such patients, are yet to be clarified.

Methods

This ongoing trial is a multicenter, prospective, observational study of non-dialysis CKD patients with renal anemia. The primary objective is to survey the current realities of the therapy with ESA in Japan and evaluate the correlation between hyporesponsiveness to darbepoetin alfa and CKD progression. The secondary objective is to investigate relationship between ESA hyporesponsiveness and CVD events based on the clinical situation in Japan, and to explore an ESA response index.

Results

The subjects consist of CKD patients with estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m² who present renal anemia. The target number of registered cases is 2000 patients, based on estimates of incidences of renal and CVD events from past studies. Renal function and CVD events will be observed for 96 weeks after the initiation of darbepoetin alfa administration. Definitions of ESA hyporesponsiveness will also be investigated.

Conclusion

By clarifying markers and factors involved in ESA hyporesponsiveness and their relationships with renal and CVD events, this ongoing study aims to improve evidence-based therapies for renal anemia in non-dialysis CKD patients.

     

Sirolimus: efficacy in liver transplant patients with nephrotoxicity and renal insufficiency

Nephrotoxicity is a complication of patients undergoing orthotopic liver transplantation. Herein we present several factors that play an important role in this complication.     

Effects of atorvastatin on renal function in patients with dyslipidemia and chronic kidney disease: Rationale and design of the ASsessment of clinical Usefulness in CKD patients with Atorvastatin (ASUCA) trial

Background

Since dyslipidemia has been shown to be an independent risk factor for the progression of chronic kidney disease (CKD), low-density lipoprotein cholesterol (LDL-C)-lowering therapy can be potentially associated with inhibition of CKD progression. The ASsessment of clinical Usefulness in CKD patients with Atorvastatin (ASUCA) trial was designed to determine whether atorvastatin has protective effects on renal function in patients with dyslipidemia and CKD.

Methods

We decided to carry out a prospective multi-center, open-labeled, randomized trial to compare the reno-protective effects between diet therapy alone and atorvastatin plus diet therapy in patients with dyslipidemia (LDL-C ≥ 140 mg/dL if not treated or LDL-C ≥ 100 mg/dL if treated with lipid-lowering drugs in subjects taking dyslipidemia-treating agents other than statins) and CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²]. The primary endpoint is the change in eGFR (mL/min/1.73 m²) as calculated by the modified MDRD equation for Japanese after 2 years of treatment.

Results

Enrollment began in April 2009 and was completed in March 2011. A total of 334 patients (213 male and 121 female) were randomly assigned to either diet therapy alone or atorvastatin plus diet therapy and included in an intent-to-treat population. In the atorvastatin and control groups, the mean ages were 63.2 and 63.1 years, mean eGFRs were 55.9 and 54.0 mL/min/1.73 m², and median urinary albumin/creatinine ratios were 24.9 and 29.1 mg/g, respectively.

Conclusions

This study distinguishes itself from similar studies by increasing statistical accuracy derived from its significantly larger sample size and longitudinal magnitude. The results of this study will help to determine whether atorvastatin has reno-protective effects in patients with dyslipidemia and CKD.     

极低蛋白饮食治疗严重慢性肾功能不全的安全性和有效性

目的观察在不补充必需氨基酸或其酮酸情况下,极低蛋白饮食对严重慢性肾功能不全患者营养状态及肾功能的影响.方法37例慢性肾功能不全患者[Scr(588.2±123.5)μmol/L,Ccr(9.77±3.48)ml@min-1@(1.73m2)-1]按实际蛋白摄入量分成两组极低蛋白饮食治疗组[VLPD,蛋白摄入量(0.33±0.04)g@kg-1@d-1],20例;低蛋白饮食治疗组[LPD,蛋白质摄人量为(0.60±0.11)g@kg-1@d-1],17例.观察患者的顺应性、营养相关生化指标及肾功能进展.结果(1)患者对极低蛋白饮食有较好的耐受性,无一例患者出现蛋白营养不良征象,观察期间患者血清白蛋白浓度稳定.和低蛋白饮食相比,极低蛋白饮食患者血清白蛋白浓度升高(P＜0.05).5例VLPD患者虽然蛋白质摄入量持续低于0.3 g@kg-1@d-1,但经过最长53个月治疗,血清白蛋白仍能维持正常范围.(2)虽然两组患者血清转铁蛋白浓度有下降趋势,但仍保持在正常范围.(3)和VLPD组比较,LPD组患者血HCO3-水平明显降低(P＜0.05),且VLPD组患者为治疗代谢性酸中毒所使用的碳酸氢盐剂量明显低于LPD组(P＜0.05).(4)两组患者血清磷浓度保持正常,LPD组增高趋势较明显,但差异无显著性意义(P＞0.05).VLPD组服用肠道磷结合剂的剂量明显小于LPD组(P＜0.05).(5)VLPD及LPD组患者肾功能不全进展速度分别为(0.125±0.072)和(0.214±0.017)ml@min-1@月-1,VLPD组显著慢于LPD组(P＜0.01),而且两组患者肾功能下降速度均明显低于文献报道(平均0.3ml@min-1@月-1).在进入透析治疗阶段,VLPD组的Ccr明显低于LPD组[(3.07±1.17)vs(8.46±2.57)ml@min-1@(1.73m2)-1].LPD组患者在(33.4±6.5)个月内进入透析治疗,而VLPD组患者从治疗开始到进入透析治疗平均(72.0±33.5)个月,比LPD组推迟4～5年.结论在未补充必需氨基酸或其酮酸的情况下,极低蛋白饮食治疗可以安全地用于透析导入前的慢性肾衰患者.其通过改善尿毒症消化道症状而维持患者营养状态,并能有效地纠正慢性肾衰伴随的代谢紊乱,减少合并症,从而推迟开始透析治疗时间.     

Lanthanum carbonate (Fosrenol) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease

AIMS: High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment. Lanthanum carbonate (Fosrenol) is a new non-aluminum, non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). We report data from a recent trial, which, for the first time, assessed the efficacy and tolerability of lanthanum carbonate treatment, compared with placebo, in Chinese patients with ESRD. PATIENTS AND METHODS: Following a one- to three-week washout phase and a four-week, open-label lanthanum carbonate dose-titration phase, male and female hemodialysis patients were randomized (1:1) to receive either lanthanum carbonate or placebo for four weeks. The primary efficacy parameter of the study was the control of serum phosphorus levels (< or =1.8 mmol/l [< or = 5.6 mg/dl]). Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone, calcium, and calcium x phosphorus (Ca x P) product levels. The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study. RESULTS: Mean serum phosphorus level at the end of washout was 2.5 +/- 0.5 mmol/l (7.7 +/- 1.5 mg/dl; n=73), and there was no evidence of a difference in levels between the treatment groups pre-randomization. At the end of the study, lanthanum carbonate-treated patients had significantly lower phosphorus levels (1.6 +/- 0.5 mmol/l [5.1 +/- 1.5 mg/dl]; n=30) than those receiving placebo (2.3 +/- 0.4 mmol/l [7.2 +/- 1.3 mg/dl]; n=31; p < 0.001). In addition, a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels (60%) compared with the placebo group (10%; p < 0.001). Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of randomized treatment (p < 0.001). Lanthanum carbonate was well tolerated; only one serious adverse event was reported, which was unrelated to treatment. CONCLUSIONS: Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD. This finding supports the results of previous US and European studies, which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels.     

Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study

Patients on cyclosporin A (CsA) often develop hyperuricaemiaand gout. In transplant patients the use of uricosuric drugsfor treating hyperuricaemia may be preferable to allopurinolbecause of the known interaction of the latter with azathioprine.We therefore prospectively studied the uricosuric efficacy of100 mg benzbromarone (Bbr;Desuric®) daily in 25 CsA-treatedrenal transplant patients with stable graft function and hyperuricaemia(>359 µmol/l for females, >491 µmol/l formales). Benzbromarone decreased plasma uric acid from 579±18µmol/l to 313±24 µmol/l (mean±SEM;P<0.001) and thereby normalized plasma uric acid in 21 of25 patients. The remaining four patients had creatininc clearancesbetween 21 and 25 ml/min, the lowest of the entire study group.Mean fractional clearance of uric acid increased from 5.4±0.4%to 17.2±1.0% (P<0.001). The relative decrease of plasmauric acid closely correlated with baseline creatinine clearance(r=0.67; P<0.001). CsA trough values were not influenced.None of the patients experienced any significant side-effects.As an unexpected find-ing, urinary uric acid excretion increasedfrom 2082 ± 175 µmol7sol;24 h to 3233 ±232µmol/24 h after 4 weeks' treatment with benzbromarone. In conclusion, benzbromarone normalized plasma uric acid inall CsA-treated renal transplant recipients with a creatinineclearance >25 ml/min. Due to its excellent efficacy and lackof significant side-effects, benzbromarone appears to be preferableto allopurinol in CsA-treated renal transplant recipients witha creati nine clearance over 25 ml/min.     

Rationale and design of the INNOVATE Trial: an international cooperative study on surgical versus conservative treatment for odontoid fractures in the elderly

Background

The purpose of this study was the development of a valid and reliable “Mechanical and Inflammatory Low Back Pain Index” (MIL) for assessment of non-specific low back pain (NSLBP). This 7-item tool assists practitioners in determining whether symptoms are predominantly mechanical or inflammatory.

Methods

Participants (n?=?170, 96 females, age?=?38?±?14 years-old) with NSLP were referred to two Spanish physiotherapy clinics and completed the MIL and the following measures: the Roland Morris Questionnaire (RMQ), SF-12 and “Backache Index” (BAI) physical assessment test. For test-retest reliability, 37 consecutive patients were assessed at baseline and three days later during a non-treatment period. Face and content validity, practical characteristics, factor analysis, internal consistency, discriminant validity and convergent validity were assessed from the full sample.

Results

A total of 27 potential items that had been identified for inclusion were subsequently reduced to 11 by an expert panel. Four items were then removed due to cross-loading under confirmatory factor analysis where a two-factor model yielded a good fit to the data (χ2?=?14.80, df?=?13, p?=?0.37, CFI?=?0.98, and RMSEA?=?0.029). The internal consistency was moderate (α?=?0.68 for MLBP; 0.72 for ILBP), test-retest reliability high (ICC?=?0.91; 95%CI?=?0.88-0.93) and discriminant validity good for either MLBP (AUC?=?0.74) and ILBP (AUC?=?0.92). Convergent validity was demonstrated through similar but weak correlations between the ILBP and both the RMQ and BAI (r?=?0.34, p?<?0.001) and the MLBP and BAI (r?=?0.38, p?<?0.001).

Conclusions

The MIL is a valid and reliable clinical tool for patients with NSLBP that discriminates between mechanical and inflammatory LBP.     

The superior approach with the stomach roll-up technique improves intraoperative outcomes and facilitates learning laparoscopic distal pancreatectomy: a comparative study between the superior and inferior approach

Surgery Today - We introduced a superior approach and a unique technique to retract the stomach, called the “stomach roll-up technique”, to standardize laparoscopic distal...     

Safety and efficacy of atorvastatin in patients with severe renal dysfunction

OBJECTIVE: To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. MATERIAL AND METHODS: This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. RESULTS: The follow-up period was a mean of 20+/-14.4 months (range 1-36 months) for those on atorvastatin versus 22+/-12.7 months (range 0.5-36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; -23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; -35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1-30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. CONCLUSION: Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.     

舒尼替尼在晚期肾细胞癌治疗中的运用

目的：探讨苹果酸舒尼替尼对晚期肾细胞癌治疗的安全性和有效性。方法：晚期肾细胞癌患者22例,男18例,女4例,平均年龄56岁,均为转移性或难以手术的肾细胞癌患者。采用舒尼替尼治疗,其中18例为一线治疗,4例为二线治疗。均为单一服药,口服50mg／d,每4周停药2周者16例;口服37．5mg／d,连续服药者6例。持续用药至肿瘤进展或出现不可耐受的并发症。以6周为1个治疗周期,至少每2个治疗周期进行疗效评价。结果：1例患者服药不足2周期内死亡,可评价病例21例。部分缓解6例（28．6％）,疾病稳定13例（61．9％）,疾病进展2例（9．5％）,无完全缓解病例。常见的不良反应包括手足皮肤反应、皮疹、疲劳乏力、骨髓抑制、味觉变化等。结论：舒尼替尼治疗晚期肾癌患者效果确切,不良反应多数可控制,但对于KPS评分较低,一般情况差,肿瘤负荷大的患者,运用时需慎重。     

非布司他与别嘌醇治疗慢性肾脏病合并高尿酸血症的疗效比较

目的探讨非布司他与别嘌醇在治疗慢性肾脏患者合并高尿酸血症的临床疗效分析比较。方法回顾性分析2013年1月至2015年2月中国人民解放军第174医院收治的78例慢性肾脏病合并高尿酸血症患者,并根据治疗方法将其分为对照组和治疗组。2组患者均采用优质低蛋白饮食、降压[钙通道阻滞剂和(或)β受体阻滞剂]、纠正贫血(促红细胞生长素)、补充α酮酸(开同)及纠正水、电解质酸碱平衡(碳酸氢钠)等综合治疗;观察组加用非布司他20 mg/d,对照组加用别嘌醇100 mg/d;2组均治疗观察24周。分析治疗前后2组患者血肌酐、血尿酸及临床疗效,并进行统计学分析。结果 2组治疗前后实验室相关指标比较结果表明2组治疗后血尿酸与治疗前比较,均有显著改善(均P0.05),且治疗组患者治疗后尿酸与对照组行组间比较有统计学差异(P0.05)。治疗组治疗后血肌酐与治疗前比较明显降低,有统计学差异(P0.05);而对照组治疗前后血肌酐无明显变化(P0.05)。治疗组临床总有效率高于对照组(P0.05)。2组均未发现明显的不良反应。结论非布司他相对于别嘌醇降低血尿酸水平的作用更强,且可改善肾功能,药物不良反应较小,因此在治疗慢性肾脏合并高尿酸血症患者上具有良好的应用前景。     

A phase II study of the efficacy and safety of AMG 102 in patients with metastatic renal cell carcinoma

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? It is now recognized that all patients with mRCC will eventually become resistant to VEGF inhibition. Although existing level 1 evidence supports the use of second‐line therapy, the oral mTOR inhibitor Everolimus, recent data also indicates that sequential VEGF inhibition is an appropriate therapeutic manoeuver in this cohort of patients. Targeting the alternative signaling pathway of Hepatocyte growth factor/c‐met can lead to anti‐tumour activity in RCC. AMG‐102 is a fully human monoclonal antibody to HGF/SF that prevents HGF/SF from binding to c‐Met and blocks signaling pathways that drive tumour‐cell proliferation, migration, invasion and survival. It emphasizes the need to continue exploring new therapeutic targets in RCC.

OBJECTIVE

? To evaluate the efficacy and safety of single‐agent AMG 102, an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor (HGF/SF), in renal cell carcinoma (RCC).

PATIENTS AND METHODS

? This open‐label phase II study included patients ≥18 years old with histologically confirmed, advanced or metastatic RCC (mRCC) and Eastern Cooperative Oncology Group performance status 0 to 2. AMG 102 was administered i.v. at 10 or 20 mg/kg once every 2 weeks. ? A two‐stage design was used at each dose level and the primary endpoint was objective best confirmed response (by Response Evaluation Criteria in Solid Tumours) at any time.

RESULTS

? Sixty‐one patients with mRCC enrolled and received AMG 102 (40 at 10 mg/kg; 21 at 20 mg/kg). Overall, 70.5% were men, median age was 59 years (range, 39 to 84 years), and 92% had received previous anti‐vascular endothelial growth factor therapy. RCC histologies were: clear cell (75.4%), papillary (11.5%), chromophobe (4.9%) and unclassified (8.2%). ? One confirmed partial response occurred at 10 mg/kg, maintained for over 2.5 years; 26 patients (43%) had stable disease, 10 (16%) for ≥32 weeks. The median profression‐free survival was 3.7 months at 10 mg/kg and 2.0 months at 20 mg/kg. The commonest adverse events were oedema (45.9%), fatigue (37.7%) and nausea (27.9%). Grade 3 or 4 adverse events occurred in 33% of patients, the most common being oedema (9.8%). ? Baseline levels of plasma HGF/SF and soluble c‐Met as well as archival‐tumour c‐Met did not correlate with measures of efficacy.

CONCLUSION

? Single‐agent AMG 102 was tolerable, but it is unclear if AMG 102 was growth inhibitory in this population of patients with mRCC.