VEGF inhibitors in metastatic renal cell carcinoma: current therapies and future perspective

Metastatic renal cell carcinoma (RCC) is predominantly refractory to treatment with traditional cytotoxic chemotherapies, and until recently management options were limited to immunotherapy, palliative care, or phase I trials. The past five years have witnessed a major change in the treatment of advanced RCC with the introduction of targeted therapies that derive their efficacy through affecting angiogenesis. The main class of agents involves drugs that target the vascular endothelial growth factor (VEGF). Several VEGF inhibitors are now approved for the treatment of metastatic RCC. The field is expanding rapidly with goals including 1) developing novel more potent and better tolerated agents and 2) defining the role of combination and sequential anti-VEGF regimens.     

Management of clinical stage I nonseminomatous germ cell testicular cancer

The optimal management of patients who have clinical stage I nonseminomatous germ cell tumors remains controversial. Surveillance, retroperitoneal lymph node dissection (RPLND), and chemotherapy with two cycles of bleomycin-etoposide-cisplatin are established treatment options and all are associated with long-term cancer control rates of 97% or greater. Studies have consistently identified the presence of lymphovascular invasion and a predominant component of embryonal carcinoma in the primary tumor as risk factors for occult metastatic disease in these patients. Patients who do not have these risk factors are optimally managed by active surveillance given the low risk for relapse. For patients at high risk for relapse and who are not candidates for surveillance, we believe the evidence supports RPLND over primary chemotherapy.     

Impact of Bone and Liver Metastases on Patients with Renal Cell Carcinoma Treated with Targeted Therapy

Background

The skeleton and liver are frequently involved sites of metastasis in patients with metastatic renal cell carcinoma (RCC).

Objective

To analyze outcomes based on the presence of bone metastases (BMs) and/or liver metastases (LMs) in patients with RCC treated with targeted therapy.

Design, setting, and participants

We conducted a review from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) of 2027 patients with metastatic RCC.

Outcome measurements and statistical analysis

We analyzed the impact of the site of metastasis on overall survival (OS) and time-to-treatment failure. Statistical analyses were performed using multivariable Cox regression.

Results and limitations

The presence of BMs was 34% overall, and when stratified by IMDC risk groups was 27%, 33%, and 43% in the favorable-, intermediate-, and poor-risk groups, respectively (p < 0.001). The presence of LMs was 19% overall and higher in the poor-risk patients (23%) compared with the favorable- or intermediate-risk groups (17%) (p = 0.003). When patients were classified into four groups based on the presence of BMs and/or LMs, the hazard ratio, adjusted for IMDC risk factors, was 1.4 (95% confidence interval [CI], 1.22–1.62) for BMs, 1.42 (95% CI, 1.17–1.73) for LMs, and 1.82 (95% CI, 1.47–2.26) for both BMs and LMs compared with other metastatic sites (p < 0.0001). The prediction model performance for OS was significantly improved when BMs and LMs were added to the IMDC prognostic model (likelihood ratio test p < 0.0001). Data in this analysis were collected retrospectively.

Conclusions

The presence of BMs and LMs in patients treated with targeted agents has a negative impact on survival. Patients with BMs and/or LMs may benefit from earlier inclusion on clinical trials of novel agents or combination-based therapies.     

不同胰岛素促泌剂单药治疗对2型糖尿病患者死亡率和心血管风险的影响

研究纳入丹麦1997～2006年间107806例起始胰岛素促泌剂或二甲双胍单药治疗的2型糖尿病患者(年龄>20岁,没有使用过胰岛素单药和联合治疗)其中9607例患者既往存在心肌梗死史.随访时间3.3年,每3个月为一个区间,收集不同胰岛素促泌剂或二甲双胍的处方,如果某区间无处方量则以之前最多3个处方量的区间 作为参考.