The Blood Neutrophil-to-lymphocyte Ratio Predicts Survival in Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib

Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poorsurvival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate theprognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC whoreceived sorafenib monotherapy. Methods: A total of sixty-five patients with advanced HCC, not eligible forlocoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender,tumoral characteristics, performance status and NLR were analyzed. Results: Median OS and TTP for the entirecohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLRat baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months)compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (≤4) (P=0.01). Age ≤65, NLR>4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariateanalysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors ofpoorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months)compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). Conclusions: Highbaseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib.     

Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosisand low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factorreceptor beta (PDGFR-β) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenibto life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy andside effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females)receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median agewas 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of thepatients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A totalof 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluablecases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%).Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reducedonly in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-footsyndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated betterefficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-freesurvival and overall survival findings were comparable. The side effect rates indicate that the drug was toleratedwell. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patientswith inoperable or metastatic HCC.     

白头翁皂苷D联合索拉非尼对人肝癌细胞侵袭与转移的影响

[摘要]目的 探讨白头翁皂苷D联合索拉非尼对人肝癌细胞株侵袭与转移的影响。 方法 将人肝癌细胞BEL-7402分为白头翁皂苷D单药处理组、索拉非尼单药处理组及两药联合处理组,观察比较三种处理方式对肝癌细胞侵袭和转移的影响。结果 检测分析各组黏附抑制率,作用3h,索拉非尼组显著高于白头翁皂苷D组（P＜0.05或＜0.01）,联合用药组显著高于索拉非尼组和白头翁皂苷D组（P＜0.01）;作用5h,白头翁皂苷D组黏附抑制率显著高于索拉非尼组（P＜0.01）,并且高于白头翁皂苷D组作用3h（P＜0.01）,说明两药联合对肝癌细胞的黏附抑制率具有协同作用（Q=2.33＞1.15）;检测分析各组迁移抑制率,索拉非尼单药组和两药联合组对肝癌细胞的迁移抑制率均显著高于白头翁皂苷D单药组（P＜0.01）,并且两药联合组的抑制率显著高于索拉非尼单药组（P＜0.01）,说明两药联合对肝癌细胞的迁移抑制作用具有协同作用（Q=1.39＞1.15）;检测分析侵袭抑制率,索拉非尼单药组和两药联合组均显著高于白头翁皂苷D组（P＜0.01）,说明两药联合对肝癌细胞的侵袭抑制作用具有拮抗作用（Q=0.68＜0.85）。各组的VEGF-C、MMP-9表达情况：白头翁皂苷D单药组的MMP-9表达水平显著下降,索拉非尼组和两药联合组的VEGF-C、MMP-9及表达水平均显著下降（P＜0.05）;与白头翁皂苷D单药组比较,两药联合组的VEGF-C表达水平显著下降;两药联合组较白头翁皂苷D单药组VEGF-C水平显著下降（P＜0.05）。结论 白头翁皂苷D、索拉非尼单药以及两药联合对肝癌细胞BEL-7402细胞株的黏附、迁移、侵袭具有一定的抑制作用,且二者对肝癌细胞的黏附、迁移的抑制具有协同作用。     

Is the efficacy of sorafenib treatment in patients with hepatocellular carcinoma affected by age?

Cancer is a prevalent disease in the elderly population and hepatocellular carcinoma (HCC) is a major health problem among all tumors. Curative treatments for early-stage include liver transplantation, resection and percutaneous ablation. Transarterial chemoembolization (TACE) and sorafenib, classified as non-curative treatments, can improve survival for patients with intermediate and advanced tumors, respectively. Even if the incidence of HCC progressively increases with advanced age in all populations, reaching a peak at 70 years, few reports concerning correct management of HCC in elderly patients exist. Moreover, data from large randomized controlled trials (RCT) poorly reflect the elderly population that is often quantitatively and qualitatively underrepresented, as a result of the presence of tight enrolment criteria. The aim of this brief review is to highlight the main concerns, pitfalls and warnings regarding the management of HCC in elderly patients, with particular focus on systemic therapy with sorafenib.     

Intraarterial therapies for primary liver cancer: state of the art

Image-guided intraarterial therapies play an important role in the treatment of patients with hepatic malignancies. These therapies provide the dual benefit of reduced systemic toxicity and effective local tumor control. As a result, procedures such as transarterial chemoembolization have been included in the official treatment guidelines for hepatocellular carcinoma (HCC) and are fully accepted for the treatment of patients with intermediate stage disease. In this review, we will describe the scientific rationale for intraarterial therapies and discuss the available clinical evidence for primary liver cancer. Finally, we will touch on the current trends consisting of combining intraarterial approaches with systemically administered targeted agents.     

Advanced kidney cancer: treating the elderly

Advancing age represents the primary risk factor for renal tumors. Despite findings on the inhibition of angiogenesis that have led to six new drugs to treat metastatic renal cell carcinoma, elderly patients have not been fully represented in clinical trials. In addition, current opinions regarding nephrectomy in elderly patients are conflicting. Available data refer to the efficacy and safety of sorafenib, sunitinib, everolimus, bevacizumab and temsirolimus in patients aged 65 years and older; safety and efficacy data are available only for sunitinib, sorafenib,and everolimus in patients aged 70 years and older and only sorafenib has safety data for patients aged 75 years and older. A different approach based on evaluating comorbidities at baseline, risk of drug interactions and the impact of antitumor treatment in patients with polytherapy regimen is discussed. A decision-making algorithm is proposed to facilitate the selection of the best therapy for kidney tumors for a specific elderly patient profile.     

Korean Red Ginseng Extract Enhances the Anticancer Effects of Sorafenib through Abrogation of CREB and c‐Jun Activation in Renal Cell Carcinoma

Although application of sorafenib in the treatment of human renal cell carcinoma (RCC) remains one of the best examples of successful targeted therapy, majority of RCC patients suffer from its side effects as well as develop resistance to this targeted therapy. Thus, there is a need to promote novel alternative therapies for the treatment of RCC. In this study, we investigated whether Korean red ginseng extract (KRGE) could inhibit the proliferation and induce chemosensitization in human renal cancer cells. Also, we used a human phospho‐antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after KRGE and sorafenib combination treatment. Korean red ginseng extract suppressed the proliferation of two RCC cell lines; activated caspase‐3; caused poly(ADP‐ribose) polymerase cleavage; abrogated the expression of B‐cell lymphoma 2, B‐cell lymphoma extra large, survivin, inhibitors of apoptosis proteins‐1/2, cyclooxygenase‐2, cyclin D1, matrix metallopeptidase‐9, and vascular endothelial growth factor; and upregulated pro‐apoptotic gene products. Interestingly, KRGE enhanced the cytotoxic and apoptotic effects of sorafenib in RCC cells. The combination treatment of KRGE and sorafenib more clearly suppressed cyclic adenosine monophosphate response element‐binding protein and c‐Jun phosphorylation and induced phosphorylation of p53 than did the individual treatment regimen. Our results clearly demonstrate that KRGE can enhance the anticancer activity of sorafenib and may have a substantial potential in the treatment of RCC. Copyright © 2017 John Wiley & Sons, Ltd.     

Phase 2 trial of sorafenib in patients with advanced urothelial cancer

BACKGROUND:

There is no effective second‐line systemic chemotherapy for patients with disease progression after cisplatin‐based chemotherapy. A phase 2 trial of sorafenib was performed to determine the activity and toxicity of this agent in a multi‐institutional setting in patients previously treated with 1 prior chemotherapy regimen.

METHODS:

Twenty‐seven patients with advanced urothelial carcinoma were treated with sorafenib 400 mg orally twice daily continuously until progression or unacceptable toxicity.

RESULTS:

There were no objective responses observed. The 4‐month progression‐free survival (PFS) rate was 9.5%; median overall survival of the group was 6.8 months. There were no therapy‐related deaths, and common grade 3 toxicities included fatigue and hand‐foot syndrome.

CONCLUSIONS:

Although sorafenib as a single agent has minimal activity in patients with advanced urothelial cancer in the second‐line setting, further investigation of tyrosine kinase inhibitors using different trial designs with PFS endpoints is warranted. Cancer 2009. © 2009 American Cancer Society.