Treatment of everolimus-resistant metastatic renal cell carcinoma with VEGF-targeted therapies

Background:

Treatment of everolimus-resistant disease remains largely undefined in metastatic renal cell carcinoma (mRCC). We report on 40 patients (pts) who receive systemic treatment after failure of everolimus.

Patients and methods:

Forty pts received sunitinib (n=19), sorafenib (n=8), dovitinib (n=10) or bevacizumab/interferon (n=3) after failure of everolimus. Median progression-free survival (PFS), overall survival (OS) and best tumour response (according to Response Evaluation Criteria In Solid Tumors) were analysed retrospectively. Kaplan–Meier, log-rank test and Cox regression analyses were used to estimate or predict OS and PFS.

Results:

Treatment of everolimus-resistant disease was associated with a PFS of 5.5 months. (range 0.4–22.3) and an objective partial remission (PR) in 4 pts (10%) and stable disease (SD) in 22 pts (55%). In univariate analyses, first-line treatment with sorafenib was the only variable to correlate with a prolonged PFS of treatment in everolimus-resistant disease (P=0.036). However, its significance as a predictive marker for subsequent therapy could not be verified in multivariate analyses.

Conclusions:

Vascular endothelial growth factor targeted therapy shows promising activity in everolimus-resistant metastatic renal cancer and warrants further studies.     

Sorafenib with interleukin-2 vs sorafenib alone in metastatic renal cell carcinoma: the ROSORC trial

Background:

Preclinical investigations support combining sorafenib with IL-2 in the treatment of metastatic renal cell carcinoma (mRCC).

Methods:

In this open-label, phase II study, 128 patients with mRCC were randomised to receive oral sorafenib, 400 mg twice daily, plus subcutaneous IL-2, 4.5 million international units (MIU) five times per week for 6 in every 8 weeks, or sorafenib alone. After enrolment of the first 40 patients, IL-2 dose was reduced to improve the tolerability.

Results:

After a median follow-up of 27 months, median progression-free survival (PFS) was 33 weeks with sorafenib plus IL-2, and 30 weeks with sorafenib alone (P=0.109). For patients receiving the initial higher dose of IL-2, median PFS was 43 weeks vs 31 weeks for those receiving the lower dose. The most common adverse events were asthenia, hand–foot syndrome, hypertension, and diarrhoea. Grade 3–4 adverse events were reported for 38 and 25% of patients receiving combination and single-agent treatment, respectively.

Conclusion:

The combination of sorafenib and IL-2 did not demonstrate improved efficacy vs sorafenib alone. Improvements in PFS appeared greater in patients receiving higher-dose IL-2.     

监测肾癌患者外周血CD4~+CD25~+调节性T细胞在术后免疫治疗中的作用

目的:探讨肾癌患者外周血CD4+CD25+T淋巴细胞的监测在术后辅助免疫治疗中的作用。方法:将24例肾癌患者随机分为两组:A组,根治性肾切除术后行IFN-α辅助免疫治疗;B组,单纯行根治性肾切除术;C组,10例健康对照。分别在术前、术后1周以及术后3个月免疫治疗结束时采集外周血样本,流式细胞仪检测CD4+、CD8+、CD4+CD25、CD4+CD25high T淋巴细胞亚群含量,并计算各部分比值。结果:A、B组术前CD4+CD25+、CD4+CD25high T淋巴细胞亚群总体上增加,并且其含量随肿瘤分期的进展而增加(P<0.05),但部分患者并不高于健康对照组。免疫治疗后,肾癌患者CD4+CD25+T淋巴细胞总体略有上升,但术前较高的患者中,约2/3下降。结论:利用流式细胞仪监测肾癌患者外周血CD4+CD25+T淋巴细胞亚群可反映机体抗肿瘤免疫状态,有助于预测免疫治疗的预后,为肾癌尤其是早期肾癌术后辅助免疫治疗的选择提供参考。     

Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab

BACKGROUND:

Bevacizumab and sunitinib are standard initial therapy in metastatic renal cell carcinoma (mRCC). Despite common use, the safety and activity of sorafenib in bevacizumab‐ or sunitinib‐refractory mRCC have not been prospectively investigated.

METHODS:

Metastatic RCC patients with Response Evaluation Criteria in Solid Tumors (RECIST)‐defined disease progression (PD) after treatment with either bevacizumab or sunitinib received twice daily 400 mg of sorafenib in a multicenter, prospective phase 2 study. Dose escalation was permitted in the absence of significant toxicity. The primary endpoint was tumor burden reduction rate, defined as the proportion of patients with ≥5% reduction in the sum of RECIST‐defined target lesions without other PD. Secondary endpoints included progression‐free survival (PFS), duration of response, overall survival, and safety. A 2‐stage accrual design was used to test the alternative hypothesis that the tumor burden reduction rate was >20% versus <5%.

RESULTS:

Forty‐eight patients were enrolled. The tumor burden reduction rate was 30% (95% confidence interval [CI], 17%‐45%). One unconfirmed objective partial response was observed. The median PFS was 4.4 months (95% CI, 3.6‐5.9). There was no association of PFS and tumor shrinkage with response to prior therapy. Most treatment‐related adverse events were of mild‐to‐moderate intensity, and included fatigue, hypertension, diarrhea, and palmoplantar erythrodysesthesia (PPE). Patients previously treated with bevacizumab tended to develop more PPE (P = .03) and mucositis (P = .06), whereas sunitinib‐treated patients tended to develop more skin rash (P = .06).

CONCLUSIONS:

Administration of sorafenib is safe and feasible in patients with mRCC refractory to either bevacizumab or sunitinib. Modest clinical activity was observed supporting current practice patterns of sequential vascular endothelial growth factor‐targeted therapy in mRCC. Cancer 2010. © 2010 American Cancer Society.     

Sequential therapy with sorafenib and sunitinib in renal cell carcinoma

BACKGROUND:

Sunitinib and sorafenib are small‐molecule tyrosine kinase inhibitors (TKI) with antitumor activity in advanced renal cell carcinoma. A retrospective study was conducted to assess the response of renal cell carcinoma to sequential treatment with these two agents.

METHODS:

Tumor response was evaluated by using Response Evaluation Criteria In Solid Tumors (RECIST) criteria in patients failing first‐line therapy with either sunitinib or sorafenib and subsequently receiving second‐line therapy with the other TKI agent.

RESULTS:

Twenty‐nine patients received sorafenib followed by sunitinib (Group A), and 20 patients received sunitinib followed by sorafenib (Group B). TKI drugs were terminated in 6 (12%) patients in Group A and 4 (8%) in Group B because of toxicity. Median duration of stable disease for Groups A and B was 20 and 9.5 weeks, respectively. Median time from starting first TKI to disease progression after second TKI (time to progression) in Groups A and B was 78 and 37 weeks, respectively. Multivariate analysis revealed that Group B had a shorter time to progression than Group A (risk ratio [RR] 3.0; P = .016). Median overall survival was 102 and 45 weeks in Groups A and B, respectively (P = .061).

CONCLUSIONS:

The longer duration of disease control in patients who received sorafenib followed by sunitinib warrants further investigation. Cancer 2009. © 2008 American Cancer Society.     

New drug therapies for advanced renal cell carcinoma

The incidence of renal cell cancer is increasing and surgery is the only curative treatment for patients presenting with localized disease at diagnosis. The treatment of metastatic renal cell cancer is palliative and, until recently, immunotherapy has been the standard treatment approach with response rates between 10 and 20%. An increase in the appreciation of the biology of this disease has resulted in a number of new ‘targeted’ therapies being developed. Most notable is the introduction of tyrosine kinase inhibitors with significant activity in both treatment-naive and cytokine-refractory renal cell cancer. Drugs targeting angiogenic pathways also appear promising. These agents are being rapidly introduced into clinical practice, but further studies are needed to establish their optimal place in the management of renal cell cancer and, in particular, the role of combination and/or sequential therapy.     

Sorafenib reveals efficacy in sequential treatment of metastatic renal cell cancer

Metastatic renal cell carcinoma (mRCC) is a highly vascularized tumor with a generally poor prognosis. It is largely resistant to conventional cancer treatment, including most schemes of hormonal and cytokine therapy as well as to modern chemotherapy. Although IFN-α has been the first choice in mRCC treatment strategies for more than a decade, recent recommendations of the European Association of Urology focus on so-called molecular-targeted therapies, with multikinase inhibitors, such as sorafenib and sunitinib, blocking the progression of cell proliferation and tumor angiogenesis, as preferential therapy. Sorafenib targets the VEGF receptor, the PDGF receptor β and, finally, Raf kinase, and is approved for patients who have either received cytokines or are unsuitable for such a therapy. Although targeted therapies reveal superior efficacy compared with previous cytokine-based approaches, they do not cure patients with metastatic disease. Therefore, following tumor progression, most patients require a second-line or sequential therapy during the further progress of the disease. Owing to the fact that optimal sequencing of these new agents has not been fully elucidated, some recent mainly retrospective studies compared the sequence of sorafenib and sunitinib in order to assess the best clinical benefit in mRCC patients. Apparently, no cross-resistance could be observed in any trial, and most results demonstrated a superior efficacy of a sequence strategy when sorafenib was applied as first-line treatment. Regarding current investigations, the aim of the present article is to address and critically discuss the clinical data concerning the efficacy of sorafenib as part of a sequential treatment of mRCC.     

Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma

BACKGROUND:

This study was designed to evaluate the impact of tyrosine kinase inhibitors (TKIs) on incidence of brain metastasis (brain metastasis) and overall survival (OS) in patients with metastatic renal cell cancer (mRCC).

METHODS:

All patients who presented with mRCC but no brain metastasis in the intervals 2002 to 2003 and 2006 to 2007 were identified using the institutional tumor registry. The following data were collected: age, sex, Fuhrman grade, disease sites, nephrectomy, systemic therapy including TKIs (sorafenib or sunitinib), Memorial Sloan‐Kettering Cancer Center risk category, brain metastasis treatment, and vital status. Statistical analysis was performed using the Cox proportional hazards model and the Kaplan‐Meier method.

RESULTS:

Of the 338 patients who were identified; 154 (46%) were treated with a TKI before brain metastasis, and 184 (54%) were not. There were no significant differences in age, histology, nephrectomy, involved sites of disease other than lung, or Memorial Sloan‐Kettering Cancer Center risk category between the groups. Median OS was longer in the TKI‐treated group (25 months vs 12.1 months, P < .0001). In multivariate analysis, TKI treatment (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.38‐0.74; P < .001) was associated with improved OS. Forty‐four (13%) patients developed a brain metastasis, including 29 (15.8%) of the non‐TKI group and 15 (9.7%) of the TKI group. The 5‐year actuarial rate of brain metastasis was 40% versus 17%, respectively (P < .001). TKI treatment was associated with lower incidence of brain metastasis in Cox multivariate analysis (HR, 0.39; 95% CI, 0.21‐0.73; P = .003). Lung metastasis increased the risk of brain metastasis (HR, 9.61; 95% CI, 2.97‐31.1; P < .001).

CONCLUSIONS:

Treatment with TKI agents reduces the incidence of brain metastasis in mRCC. Lung metastasis is a risk factor for brain metastasis development. Cancer 2011;. © 2011 American Cancer Society.     

Developments in the use of tyrosine kinase inhibitors in the treatment of renal cell carcinoma

Introduction: Renal cell carcinoma (RCC) is among the most commonly diagnosed solid malignancies, but until recently there were few systemic treatment options for advanced disease. Since 2005, the treatment landscape has been transformed by the development of several novel systemic therapies. In particular, tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) pathway have been instrumental in improving outcomes in patients with metastatic disease.

Areas covered: The armamentarium of TKIs available for the treatment of RCC has expanded in recent years. The most active area of research at this time is the development of treatment regimens combining newer-generation TKIs and immune checkpoint inhibitors. Emerging data point to a role for combination therapy in the frontline management of advanced RCC. Other ongoing areas of research include the use of TKIs in the adjuvant setting and the role of cytoreductive nephrectomy within a changing treatment landscape.

Expert opinion: Although TKIs and immune checkpoint inhibitors have incrementally improved outcomes for patients with advanced RCC, long-term survival remains poor. The development of regimens combining these agents represents the next step in the evolution of the field. For the clinician, this will offer exciting possibilities and novel challenges.     

A phase 1 study of everolimus and sorafenib for metastatic clear cell renal cell carcinoma

BACKGROUND:

The current study was conducted to assess the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor effect of everolimus, a mammalian target of rapamycin inhibitor, in combination with sorafenib, a tyrosine kinase inhibitor, in patients with metastatic clear cell renal cell carcinoma.

METHODS:

Sequential cohorts of patients received escalating doses of everolimus and sorafenib in 28‐day cycles in the absence of a dose‐limiting toxicity (DLT) or disease progression were examined.

RESULTS:

Twenty patients with a median age of 65 years received therapy in 3 cohorts. Dose level 1 was comprised of everolimus at a dose of 2.5 mg daily and sorafenib at a dose of 400 mg twice daily (6 patients), dose level 2 was comprised of everolimus at a dose of 5 mg daily and sorafenib at a dose of 400 mg twice daily (8 patients), and dose level 3 was comprised of everolimus at a dose of 10 mg daily and sorafenib at a dose of 200 mg twice daily (6 patients). DLTs included grade 4 (according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) hyperuricemia with grade 2 gout and grade 3 lipase associated with grade 2 pancreatitis at dose level 2, and grade 3 rash in 2 patients at dose level 3. Dose level 2 (everolimus at a dose of 5 mg daily and sorafenib at a dose of 400 mg twice daily) was established as the maximum tolerated dose. Treatment‐related adverse events occurring in >20% of patients included diarrhea, hand‐foot syndrome, hypertension, hypophosphatemia, hypothyroidism, and rash. Five of 20 patients achieved Response Evaluation Criteria In Solid Tumors (RECIST)‐defined partial responses, all of which occurred in patients without a history of prior systemic therapy. Seven of 8 patients treated at dose level 2 experienced a partial response or stable disease. Pharmacokinetic analysis revealed no interaction between everolimus and sorafenib.

CONCLUSIONS:

The combination of everolimus and sorafenib was associated with acceptable toxicity and evidence of antitumor activity in previously untreated patients with metastatic renal cell carcinoma. Cancer 2011;. © 2011 American Cancer Society.     

Optimizing treatment for metastatic renal cell carcinoma

With the advent of targeted antiangiogenic therapies for renal cell carcinoma (RCC), the prognosis for patients with locally advanced or metastatic disease has significantly improved. Indeed, the results of several randomized clinical trials have demonstrated that targeted therapies, such as tyrosine kinase inhibitors (TKIs), provide superior efficacy and tolerability compared with traditional cytokine-based treatments. However, TKI therapy is still associated with significant toxicities related to off-target inhibition that are detrimental to patient quality of life. The results of ongoing head-to-head trials will determine how these agents compare with each other in terms of efficacy, and whether TKIs that interact with fewer off-target kinases have improved tolerability profiles. Furthermore, examining how these agents could be integrated with surgery to provide a multimodal approach to the treatment of metastatic RCC could further improve the outlook for RCC patients.     

Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma

Background:

We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials.

Methods:

Patients ⩾18 years received oral sunitinib 50 mg per day on a 4-weeks-on–2-weeks-off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice.

Results:

A total of 4543 patients received sunitinib. Median treatment duration and follow-up were 7.5 and 13.6 months. Objective response rate was 16% (95% confidence interval (CI): 15–17). Median progression-free survival (PFS) and overall survival (OS) were 9.4 months (95% CI: 8.8–10.0) and 18.7 months (95% CI: 17.5–19.5). Median PFS in subgroups of interest: aged ⩾65 years (33%), 10.1 months; Eastern Cooperative Oncology Group performance status ⩾2 (14%), 3.5 months; non-clear cell histology (12%), 6.0 months; and brain metastases (7%), 5.3 months. OS was strongly associated with the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model (n=4065). The most common grade 3/4 treatment-related adverse events were thrombocytopenia (10%), fatigue (9%), and asthenia, neutropenia, and hand–foot syndrome (each 7%).

Conclusion:

Final analysis of the sunitinib expanded-access trial provided a good opportunity to evaluate the long-term side effects of a tyrosine kinase inhibitor used worldwide in mRCC. Efficacy and safety findings were consistent with previous results.     

肾癌术后免疫治疗T细胞亚群检测及疗效观察

目的:检测肾癌术后患者IL-2免疫治疗前后对外周血T淋巴细胞亚群的水平影响,进一步观察其对肾癌术后患者的疗效。方法:肾癌术后患者98例随机分为两组:实验组58例采用IL-2治疗,皮下注射小剂量（60-100万IU/次）,隔日1次,共3月,以后每年方案同前1年。对照组40例只给予肾癌根治术,不予免疫治疗。应用流式细胞技术检测两组患者不同时间段（治疗前,治疗后2月、6月）外周血CD3+、CD4+、CD8+、CD4+/CD8+,并进行对比研究。观察两组治疗后1年、3年生存率、生活质量(KPS)评分以及不良反应。结果:实验组与对照组CD3+、CD4+、CD4+/CD8+在治疗前无明显差异(P＞0.05),治疗后2月、6月较对照组明显升高(P＜0.05)。术后1年实验组生存率100％(58/58),对照组97.5%（39/40）,两者无明显差异(P＞0.05);术后3年实验组生存率84.5％（49/58）,明显高于对照组（67.5%,27/40)(P＜0.05)。实验组术后1年生活质量评分平均升高19.6分,3年生活质量评分平均升高11.5分,均明显高于对照组3.7分、1.4分(P＜0.05)。实验组不良反应共12例,均为一过性,未影响免疫治疗。对照组无相关不良反应。结论:肾癌根治术后应用IL-2进行免疫治疗,可以提高患者免疫水平,发挥抗肿瘤作用,提高生存率,改善生活质量,不良反应较轻。     

Primary resistance to tyrosine kinase inhibitors in patients with advanced renal cell carcinoma: state-of-the-science

Although over 70% of patients with metastatic renal cell carcinoma (RCC) respond to initial therapy with tyrosine kinase inhibitors (disease control rate 70–80%), approximately 20–30% of patients do not respond to first-line therapy and progress within ≤3 months. Understanding the mechanisms of resistance to targeted therapies is vital in the development of prospectively defined sequences and because the choice of first-line therapy determines that of second and subsequent line therapy, identification of the optimal first-line therapy is a priority for clinicians treating patients with metastatic RCC. By preselecting those patients most likely to respond to antivascular endothelial growth factor therapy, clinicians can begin to optimize therapeutic strategies. This review focuses on primary antivascular endothelial growth factor-refractory patients and the move towards individualizing treatment for RCC. The authors include a review of the growing number of studies, as yet retrospective, which provide important information on the group of primary refractory patients with advanced RCC for whom the prognosis is not good. First, the percentage of primary refractory patients (26%) is in agreement with disease control rate – the sum of objective responses and disease stabilization, observed in registration studies for a range of tyrosine kinase inhibitors. Second, the prognosis for these patients is poor as they do not respond to first-line nor to second-line therapy, and changing the mechanism of action (with inhibition of mTOR pathway) does not appear to produce additional benefits. Third and most importantly, the results of these studies demonstrate the need to better characterize the mechanism of primary resistance to current therapeutic agents with the ultimate aim of developing a therapeutic strategy for this important subgroup of patients.     

Hypothyroidism in patients with renal cell carcinoma

BACKGROUND:

Sunitinib and sorafenib are tyrosine kinase inhibitors that have important antitumor activity in metastatic renal cell carcinoma (mRCC). Hypothyroidism constitutes a commonly reported side effect of both drugs, and particularly of sunitinib. The objective of this analysis was to investigate whether the occurrence of hypothyroidism during treatment with sunitinib and sorafenib affects the outcome of patients with mRCC.

METHODS:

Eighty‐seven consecutive patients with mRCC who were to receive treatment with sunitinib or sorafenib were included in a prospective analysis. Thyroid function was assessed in each patient every 4 weeks during the first 2 months of treatment and every 2 to 4 months thereafter. Assessment included serum levels of thyroid‐stimulating hormone (TSH), tri‐iodthyronine (T3), and thyroxine (T4). Subclinical hypothyroidism was defined as an increase in TSH above the upper limit of normal (>3.77 μM/mL) with normal T3 and T4 levels.

RESULTS:

Subclinical hypothyroidism was evident in 5 patients at baseline and occurred in 30 patients (36.1%) within the first 2 months after treatment initiation. There was a statistically significant correlation between the occurrence of subclinical hypothyroidism during treatment and the rate of objective remission (hypothyroid patients vs euthyroid patients: 28.3% vs 3.3%, respectively; P < .001) and the median duration of survival (not reached vs 13.9 months, respectively; hazard ratio, 0.35; 95% confidence interval, 0.14‐0.85; P = .016). In multivariate analysis, the development of subclinical hypothyroidism was identified as an independent predictor of survival (hazard ratio, 0.31; P = .014).

CONCLUSIONS:

The current results indicated that hypothyroidism may serve as a predictive marker of treatment outcome in patients with mRCC. Thus, the interpretation of hypothyroidism during treatment with sunitinib and sorafenib as an unwanted side effect should be reconsidered. Cancer 2011. © 2010 American Cancer Society.     

Targeting angiogenesis in metastatic renal cell carcinoma

Introduction: Renal cell carcinoma (RCC), and particularly its clear cell histological subtype, is commonly characterized by genetic alterations in the Von Hippel Lindau (VHL) tumor suppressor gene, leading to a typically exasperated angiogenesis. However, other biological and genetic peculiarities contribute to differentiate this malignancy from other solid tumors, including its immunogenicity.

Areas covered: This review focuses on the present and future role of antiangiogenic drugs, administered either alone (as it has been in the past few years), or in combination with other agents (e.g. immune checkpoint inhibitors), in the treatment of metastatic RCC.

Expert commentary: Due to its peculiar pathogenesis, it is unrealistic to expect to be able to get rid of antiangiogenic agents for the treatment of this disease; however, we do expect that combinations of VEGF/VEGFRs-targeting agents with immune checkpoint inhibitors will gradually replace antiangiogenic monotherapies as the standard of care, at least in the first line setting of metastatic RCC patients. Biomarkers discovery remains the highest priority in order to further improve the percentage of patients benefitting of our treatment.     

Sunitinib-induced macrocytosis in patients with metastatic renal cell carcinoma

BACKGROUND.: Sunitinib and sorafenib are small molecules that inhibit the vascular endothelial growth factor and related receptors with substantial clinical activity reported in metastatic renal cell carcinoma (RCC). Cytopenia and macrocytosis have been described in patients treated with these agents. METHODS.: A retrospective review of all patients with metastatic RCC who were treated with sunitinib or sorafenib for at least 3 months at the Cleveland Clinic Taussig Cancer Institute was undertaken. Complete blood count (CBC) data including red blood cell indices were recorded at baseline, after 3 months of therapy, and at the end of treatment. RESULTS.: A total of 61 patients were treated with sunitinib and 37 patients were treated with sorafenib with available CBC data. In patients treated with sunitinib, the median corpuscular volume (MCV) increased significantly at 3 months compared with baseline (median increase of 5.1 femtoliters [fL]; P < .001) and continued to increase throughout treatment. Patients who developed hypothyroidism had a larger MCV increase at 3 months than patients who remained euthyroid (P = .06), although macrocytosis was observed in patients without hypothyroidism. Ten patients discontinued sunitinib therapy, and the MCV decreased in all patients within 2 to 4 months, without further intervention. Bone marrow analysis of 4 patients revealed a hypocellular bone marrow with trilineage hematopoiesis and no evidence of metastasis. There was no evidence of folate or vitamin B12 deficiency. In contrast to sunitinib, there was no change in the MCV for patients treated with sorafenib. CONCLUSIONS.: Macrocytosis was a common occurrence after treatment with sunitinib but not sorafenib in patients with metastatic RCC. Sunitinib-induced macrocytosis is reversible with drug discontinuation. Cancer 2008. (c) 2008 American Cancer Society.     

索拉非尼治疗转移性肾细胞癌20例初步结果

背景与目的:肾细胞癌是男性泌尿生殖系统的常见肿瘤之一,以往的免疫治疗和化疗的效果欠佳.小分子靶向治疗药物的出现提高了的肾细胞癌的疗效.本研究初步评价索拉非尼治疗晚期转移性肾癌的疗效和毒副反应.方法:2006年3月-2007年4月,我院门诊治疗的20例无法手术切除的转移性肾癌患者,其中男性17例,女性3例.年龄30～72岁(中位年龄53岁).所有患者曾接受原发肿瘤切除.17例曾接受免疫治疗和(或)化疗.透明细胞癌19例,乳头状癌1例.转移灶部位:肺转移16例,肝转移2例,骨转移5例,腹膜后肿瘤复发或淋巴结转移4例,肾上腺转移1例,锁骨上淋巴结转移1例.至少有1处可测量病灶.治疗时间1～12个月.结果:全组无CR或PR.15例SD(其中3例稳定时间已经近1年),其中肿瘤较治疗前缩小者有11例.2例PD(1例出现新的腹膜后淋巴结,1例出现肺部新病灶).3例服药仅1个月,尚未评估.最常见的不良反应是手足皮肤反应、脱发、腹泻和高血压.结论:索拉非尼对晚期肾癌的病情控制有较好的效果,而且其毒副作用相对全身化疗为轻,患者多可很好地耐受,可推广应用于KPS评分较差的患者.其远期疗效和副作用需要更长时间的随访.